Systems, methods, and devices for fallopian tube diagnostics

ABSTRACT

The present disclosure generally relates to devices, systems, and methods for Fallopian tube diagnostics. In some embodiments a tube may have a distal end, and a balloon may have a first end coupled to the distal end of the tube. The balloon may be disposed in the tube in a first, inverted position, may be movable to a second, everted position, and may be extendable a distance distal of the tube. An extending portion may have a proximal end coupled to a second end of the balloon. The extending portion may be disposed within the balloon in the first inverted position, and may be extendable from the second end of the balloon in the second everted position.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation in part of, and claims the benefit ofpriority to, U.S. patent application Ser. No. 15/053,568, filed Feb. 25,2016, entitled “Methods and Devices for Fallopian Tube Diagnostics,”which is a continuation-in-part of U.S. patent application Ser. No.14/764,710, filed on Jul. 30, 2015, entitled “Methods and Devices forFallopian Tube Diagnostics,” which is a national stage application ofInternational Patent Application Serial No. PCT/US2014/014472, filedFeb. 3, 2014, entitled “Methods and Devices for Fallopian TubeDiagnostics,” which claims priority to U.S. Provisional PatentApplication Ser. No. 61/873,753, filed Sep. 4, 2013, entitled “EvertingCatheter for Fallopian Tube Diagnostics,” and U.S. Provisional PatentApplication Ser. No. 61/759,783, filed Feb. 1, 2013, entitled “Methodsand Devices for Fallopian Tube Diagnostics,” the entire disclosures ofwhich applications are expressly incorporated by reference herein.

This application is a nonprovisional application of, and claims thebenefit of priority to, U.S. Provisional Application Ser. No.62/546,791, filed Aug. 17, 2017, entitled “Devices for Fallopian TubeDiagnostics,” and U.S. Provisional Application Ser. No. 62/660,512,filed Apr. 20, 2018, entitled “Methods and Devices for Fallopian TubeDiagnostics,” the entire disclosures of which applications are expresslyincorporated by reference herein.

FIELD

The present disclosure generally relates to Fallopian tube diagnostics,and in particular to systems, devices, and methods that accommodate theanatomical difficulties associated with navigation of body lumens,including the Fallopian tube, for tissue sample collection.

BACKGROUND

Ovarian cancer is a significant disease in women, in which 1 out of 72women in the United States may be diagnosed with this illness during herlifetime. In 2012, over 22,000 women in the United States were diagnosedwith ovarian cancer. Early detection of ovarian cancer may be difficultdue to a lack of effective screening tests, such that ovarian cancer maynot be diagnosed until the disease has reached advanced stages, limitingtreatment options.

Screening for ovarian cancer may typically include a surgical procedurefor obtaining cell samples for diagnosis. For example, because theovaries are intra-abdominal, laparoscopic or open surgery (laparotomy)may be performed to access the ovaries. Any surgical procedure increasesa risk to the patient, including but not limited to experiencing anadverse reaction, and/or requiring significant recovery time.Additionally, an ovary biopsy may expose the patient to additional riskof potentially spreading diseased (e.g., cancerous) cells.

Thus, there exists a need for devices and processes to allow samples tobe obtained from a Fallopian tube for evaluation of ovarian cancer in aless invasive and controlled fashion and, particularly without the needfor a skin incision. There further exists a need for securing a sampleof representative cells from the Fallopian tube with a catheter toscreen for early stage cancers.

It is with respect to these and other considerations that the presentimprovements may be useful.

SUMMARY

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to necessarily identify keyfeatures or essential features of the claimed subject matter, nor is itintended as an aid in determining the scope of the claimed subjectmatter.

According to an exemplary embodiment of the present disclosure, a devicefor Fallopian tube diagnostics may include a tube having a distal endand a balloon having a first end coupled to the distal end of the tube.The balloon may be disposed in the tube in a first, inverted position,may be movable to a second, everted position, and may be extendable adistance distal of the tube distal end such that a surface of theballoon is contactable with an inner surface of the Fallopian tube. Apush wire may have a distal end coupled to a second end of the balloon.The balloon may be movable from the first inverted position to thesecond everted position by actuation of the push wire. A surface of theballoon may include a plurality of surface features for collection,retention, or both, of a tissue sample of the inner surface of theFallopian tube.

In various of the foregoing and other embodiments of the presentdisclosure, the surface features may include a plurality of wrinklesformed in the surface of the balloon, and may have at least one ofplurality of edges, micro-ridges, or overlapping material, orcombinations thereof. A plurality of wrinkles may be formable in theballoon surface. A plurality of wrinkles in the balloon surface may beformed in the balloon surface, and may be configured to retain at leasta portion of the tissue sample after contacting the inner surface of theFallopian tube. The surface features may be etched in the surface of theballoon. A portion of the surface of the balloon may be embossed to forma plurality of peaks and valleys. The plurality of surface features mayimprove adhesion of the tissue sample to the balloon surface compared tothe balloon surface without the surface features. The balloon may beinflatable for moving the balloon from the first inverted position tothe second everted position. A filament may be attached to the pushwire, the filament may be disposed within the balloon in the firstinverted position, and the filament may be extendable from the balloonin the second everted position.

According to an exemplary embodiment of the present disclosure, a systemfor collecting a tissue sample in a body lumen may include a tube havinga distal end and a balloon having a first end coupled to the distal endof the tube and a second end coupled to a distal end of a push wire. Theballoon may be positionable in a first, inverted state. The push wiremay be configured to advance to evert the balloon to a second, evertedstate, such that the balloon extends out of the distal end of the tube.A surface of the balloon may be configured in the second, everted state,to contact an inner surface of the body lumen for transference of thetissue sample to the balloon surface. The balloon surface may include aplurality of surface features for collection, retention, or both, of thetissue sample.

In various of the foregoing and other embodiments of the presentdisclosure, the surface features may include a plurality of wrinklesformed in the surface of the balloon, having at least one of a pluralityof edges, micro-ridges, or overlapping material, or combinationsthereof. A plurality of wrinkles may be formable in the balloon surface.A plurality of wrinkles in the balloon surface may be configured toretain at least a portion of the tissue sample after contacting theinner surface of the body lumen. The surface features may be etched inthe surface of the balloon. The plurality of surface features mayimprove adhesion of the tissue sample to the balloon surface compared tothe balloon surface without the surface features.

According to an exemplary embodiment of the present disclosure, a methodfor collecting a tissue sample in a body lumen may include providing atube having a distal end and a balloon having a first end coupled to thedistal end of the tube and a second end coupled to a distal end of apush wire. The balloon may be positioned in a first, inverted state. Thepush wire may be advanced to evert the balloon to a second, evertedstate, such that the balloon extends out of the distal end of the tube.A balloon surface may contact in the second, everted state, an innersurface of the body lumen. The balloon surface may include a pluralityof surface features for collection, retention, or both, of the tissuesample.

In various of the foregoing and other embodiments of the presentdisclosure, the surface features may include a plurality of wrinklesformed in the surface of the balloon, and may have at least one of aplurality of edges, micro-ridges, or overlapping material, orcombinations thereof. A plurality of wrinkles may be formable in theballoon surface. A plurality of wrinkles in the balloon surface may beconfigured to retain at least a portion of the tissue sample aftercontacting the inner surface of the body lumen. The plurality of surfacefeatures may improve adhesion of the tissue sample to the balloonsurface compared to the balloon surface without the surface features.

According to an exemplary embodiment of the present disclosure, a devicefor Fallopian tube diagnostics may include a tube having a distal end,and a balloon having a first end coupled to the distal end of the tube.The balloon may be disposed in the tube in a first, inverted position,may be movable to a second, everted position, and may be extendable adistance distal of the tube. An extending portion may have a proximalend coupled to a second end of the balloon. The extending portion may bedisposed within the balloon in the first inverted position, and may beextendable from the second end of the balloon in the second evertedposition.

In various of the foregoing and other embodiments of the presentdisclosure, the extending portion may be any of a filament, suture, orstring, or combinations thereof. At least a portion of the filament,suture, or string, or combinations thereof, may be braided. Theextending portion may be formed of one or more filaments having a color.The colors of the one or more filaments of the extending portion mayprovide for a contrasting visualization. The extending portion mayinclude one or more knots or indicia for one or both of visual andtactile feedback. The extending portion may be a braided filamentconfigured to collect and retain a tissue sample in response toextending from the balloon in the second everted position. A push wiremay have a distal end coupled to the second end of the balloon and theproximal end of the extending portion. The balloon and the extendingportion may be movable from the first inverted position to the secondeverted position by actuation of the push wire.

According to an exemplary embodiment of the present disclosure, a systemfor collecting a tissue sample in a body lumen may include a tube havinga distal end, and a balloon may have a first end coupled to the distalend of the tube and a second end. An extending portion may be attachedto the second end of the balloon. The balloon and the extending portionmay be positionable in a first, inverted state. The balloon and theextending portion may be configured to advance to a second, evertedstate, such that the balloon and the extending portion may extend out ofthe distal end of the tube. The extending portion may be disposed withinthe balloon in the first inverted position, and may be extendable fromthe balloon in the second everted position into the body lumen.

In various of the foregoing and other embodiments of the presentdisclosure, the extending portion may be any of a filament, suture, orstring, or combinations thereof. At least a portion of the filament,suture, or string, or combinations thereof, may be braided. Theextending portion may be formed of one or more filaments having a color.The colors of the one or more filaments of the extending portion mayprovide for a contrasting visualization. The extending portion mayinclude one or more knots or indicia for one or both of visual andtactile feedback. The extending portion may be a braided filamentconfigured to collect and retain a tissue sample in response toextending from the balloon in the second everted position into the bodylumen. A push wire may have a distal end coupled to the second end ofthe balloon and the proximal end of the extending portion. The balloonand the extending portion may be movable from the first invertedposition to the second everted position by actuation of the push wire.

According to an exemplary embodiment of the present disclosure, a methodfor collecting a tissue sample in a body lumen may include providing atube having a distal end, and a balloon having a first end coupled tothe distal end of the tube and a second end. An extending portion may beattached to the second end of the balloon. The balloon and the extendingportion being may be positioned in a first, inverted state. The balloonmay be advanced to a second, everted state, such that the balloon andthe extending portion may extend out of the distal end of the tube. Theextending portion may be disposed within the balloon in the firstinverted position, and may be extendable from the balloon in the secondeverted position into the body lumen.

In various of the foregoing and other embodiments of the presentdisclosure, the tissue sample may be collected by the extending portionextendable from the balloon in the second everted position into the bodylumen. The extending portion may be any of a braided filament, braidedsuture, or braided string, or combinations thereof. The extendingportion may be formed of one or more filaments having a color. Thecolors of the one or more filaments of the extending portion may providefor a contrasting visualization. The extending portion may be a braidedfilament and may be configured to collect and retain a tissue sample inresponse to extending from the balloon in the second everted positioninto the body lumen. A push wire may have a distal end coupled to thesecond end of the balloon and the proximal end of the extending portion,and may be actuated to move the balloon and the extending portion fromthe first inverted position to the second everted position.

According to exemplary embodiments of the present disclosure, devices,systems, and methods for Fallopian tube diagnostics may include a tubehaving a distal end and a proximal end, and a sheath disposed coaxial tothe tube. A balloon may have a first end coupled to the distal end ofthe tube and a second end, and the sheath may extend over the balloon.The sheath may provide column strength to the balloon as the balloonmoves from a first, inverted position to a second, everted position,into the Fallopian tube. The sheath may minimize balloon collapse as theballoon is everted into the Fallopian tube. The sheath may protect theeverted balloon or an extended portion, or both after cell collectionduring removal from the patient. A sheath knob may connect the sheath tothe tube. The sheath knob may be configured to lock the sheath to thetube to minimize relative movement. The sheath knob may be configured tounlock the sheath from the tube for adjusting the sheath relative to theballoon and the tube.

According to exemplary embodiments of the present disclosure, devices,systems, and methods for Fallopian tube diagnostics may include one ormore markers for visualization. A first marker may be disposed on atube, and may indicate a position of the tube relative to the sheath, orsheath knob. The first marker may indicate positioning of the sheathrelative to the tube as a preparation step to cover at least a portionof a balloon in a second, everted position. The first marker mayindicate positioning of the sheath relative to the tube for initialadvancement of the balloon into the Fallopian tube. In response to atleast a portion of the balloon in the second, everted position, thesheath may be moved in a proximal direction to expose at least theportion of the balloon. A second marker may be disposed on the tube, andmay indicate a position of the tube relative to the sheath or sheathknob. The second marker may indicate positioning of the sheath relativeto the tube as a retraction marker, for visualization that the sheathcovers the everted balloon and/or extending portion after cellcollection to protect the collected cells. The second marker may bedisposed at a proximal portion of the tube. A third marker may bedisposed on a tube, and may be at a distal end of the tube relative to aconnection point of the balloon and the tube. The third marker mayvisually indicate an end of the tube, to confirm a balloon and/orextending portion extension or positioning in the Fallopian tube. Theone or more markers may be formed as a score line, a coating substance,or band of material, or combinations thereof. The one or more markersmay improve or standardize balloon positioning and extension into theFallopian tube. A seal may be disposed around a push wire and positionedrelative to a pressurized chamber 116. The push wire may be movablerelative to the seal for advancing through the tube to actuate theballoon between a first, inverted position and a second, evertedposition. In response to a leak formation between the push wire and theconical seal, a seal may be adjustable to maintain pressure for movingthe balloon between a first inverted position and a second evertedposition.

According to exemplary embodiments of the present disclosure, devices,systems, and methods for Fallopian tube diagnostics may include that atleast a portion of the sheath may be translucent, transparent, orotherwise see-through. At least a portion of the tube may betranslucent, transparent, or otherwise see-through. At least a portionof the balloon may be translucent, transparent, or otherwisesee-through. The tube may include a transparent portion and an opaqueportion. The opaque portion may be disposed at a proximal end of thetube. The transparent portion of the tube may be more flexible than theopaque portion of the tube. The transparent portion of the tube mayextend along the length and along an inner diameter of the opaqueportion of the tube. An extending portion may be connected to theballoon and may be disposed within the balloon in the first, invertedposition, and may extend from the balloon in the second, evertedposition. The extending portion may be visible through the balloon, thetube, and the sheath when in the first, inverted position. The balloonmay be inflatable by an opaque, or otherwise visible or detectable fluidfor visibility to move from the first, inverted position, to the second,everted position.

According to exemplary embodiments of the present disclosure, devices,systems, and methods for Fallopian tube diagnostics may include a handleincluding a gear mechanism for actuation of the push wire. The gearmechanism may include a plurality of gears and operable by a drivewheel. The gear mechanism may include a step-down ratio for additionalcontrol of balloon movement. The drive wheel and gear mechanism mayprovide for uniform movement of the balloon during movement between thefirst inverted position and the second everted position. In response toextending the push wire to its proximal end, the handle may include alimit mechanism for providing audible or tactile feedback to a user. Apawl may be engageable with one or more gears, for stopping gearrotation. A pawl may be biased toward a gear rack by a spring. The pawlmay engage with and slide over teeth of the gear rack for providingaudible or tactile feedback the user. The teeth may have a steeper slopeon a first side and a more moderate slope on a second side.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present disclosure are described by wayof example with reference to the accompanying figures, which areschematic and not intended to be drawn to scale. In the figures, eachidentical or nearly identical component illustrated is typicallyrepresented by a single numeral. For purposes of clarity, not everycomponent is labeled in every figure, nor is every component of eachembodiment shown where illustration is not necessary to allow those ofordinary skill in the art to understand the disclosure. In the figures:

FIG. 1 illustrates a cross-sectional view of a Fallopian tube with theuterotubal junction (UTJ) that connects the uterus to the ovaries;

FIGS. 2A-2D illustrate exemplary embodiments of a sequential insertionof an insertion catheter into a Fallopian tube in accordance with thepresent disclosure;

FIG. 3 illustrates a schematic of a hysteroscope for deploying anexemplary embodiment of a catheter in accordance with the presentdisclosure;

FIG. 4 illustrates an exemplary embodiment of a proximal introducercatheter in accordance with the present disclosure;

FIG. 5A illustrates a cross-sectional view of an exemplary embodiment ofan everting sleeve with a distal elastic balloon tip in a deflated statein accordance with the present disclosure;

FIG. 5B illustrates a cross-sectional view of the everting sleeve with adistal elastic balloon tip of FIG. 5A in an inflated state in accordancewith the present disclosure;

FIG. 6A illustrates a cross-sectional view of an exemplary embodiment ofan everting balloon with an outer construction sleeve in a deflatedstate in accordance with the present disclosure;

FIG. 6B illustrates a cross-sectional view of the everting balloon withan outer construction sleeve of FIG. 6A in an inflated state inaccordance with the present disclosure;

FIG. 6C illustrates an exemplary embodiment of an inflation of theeverting balloon with an outer construction sleeve of FIGS. 6A-6B;

FIG. 7A illustrates a cross-sectional view of an exemplary embodiment ofan everting sleeve and elastic balloon with an inelastic deliveryballoon in a deflated state in accordance with the present disclosure;

FIG. 7B illustrates a cross-sectional view of the everting sleeve andelastic balloon with an inelastic delivery balloon of FIG. 7A in aninflated state in accordance with the present disclosure;

FIG. 7C illustrates an exemplary embodiment of an inflation of theeverting sleeve and elastic balloon with an inelastic delivery balloonof FIGS. 7A-7B;

FIG. 8A illustrates a cross-sectional view of an exemplary embodiment ofan everting sleeve and elastic balloon with an irrigation lumen in adeflated state in accordance with the present disclosure;

FIG. 8B illustrates a cross-sectional view of the everting sleeve andelastic balloon with an irrigation lumen of FIG. 8A in an inflated statein accordance with the present disclosure;

FIG. 9A illustrates a cross-sectional view of an exemplary embodiment ofan everting balloon catheter in a deflated state in accordance with thepresent disclosure;

FIG. 9B illustrates a cross-sectional view of the everting ballooncatheter of FIG. 9A in an inflated state in accordance with the presentdisclosure;

FIG. 9C is an exemplary embodiment of a spiral filament in accordancewith the present disclosure;

FIG. 10A illustrates a cross-sectional view of an exemplary embodimentof an everting balloon catheter in a deflated state in accordance withthe present disclosure;

FIG. 10B illustrates a cross-sectional view of the everting ballooncatheter of FIG. 10A in an inflated state in accordance with the presentdisclosure;

FIG. 11A illustrates a cross-sectional view of an exemplary embodimentof an everting balloon catheter in a deflated state in accordance withthe present disclosure;

FIG. 11B illustrates a cross-sectional view of the everting ballooncatheter of FIG. 11A in an inflated state in accordance with the presentdisclosure;

FIGS. 11C-11D illustrate cross-sectional views of an exemplaryembodiment of an everting balloon catheter in accordance with thepresent disclosure;

FIGS. 11E-11F illustrate cross-sectional views of an exemplaryembodiment of an everting balloon catheter in accordance with thepresent disclosure;

FIG. 12A illustrates a cross-sectional view of another exemplaryembodiment of an everting balloon catheter in a deflated state inaccordance with the present disclosure;

FIG. 12B illustrates a cross-sectional view of the everting ballooncatheter of FIG. 12B in an inflated state in accordance with the presentdisclosure;

FIG. 13A illustrates a cross-sectional view of another exemplaryembodiment of an everting balloon catheter in a deflated state inaccordance with the present disclosure;

FIG. 13B illustrates a cross-sectional view of the everting ballooncatheter of FIG. 13A in an inflated state in accordance with the presentdisclosure;

FIG. 14A illustrates a cross-sectional view of another exemplaryembodiment of an everting balloon catheter in a deflated state inaccordance with the present disclosure;

FIG. 14B illustrates a cross-sectional view of the everting ballooncatheter of FIG. 14A in an inflated state in accordance with the presentdisclosure;

FIG. 15A illustrates a cross-sectional view of an exemplary embodimentof an everting balloon spiral cannula in a deflated state in accordancewith the present disclosure;

FIG. 15B illustrates the everting balloon spiral cannula of FIG. 15A inan inflated state in accordance with the present disclosure;

FIG. 16A illustrates a cross-sectional view of an exemplary embodimentof an everting distal arc balloon cannula in a deflated state inaccordance with the present disclosure;

FIG. 16B illustrates the everting distal arc balloon cannula of FIG. 16Ain an inflated state in accordance with the present disclosure;

FIG. 17A illustrates a cross-sectional view of another exemplaryembodiment of an everting balloon catheter in a deflated state inaccordance with the present disclosure;

FIG. 17B illustrates the everting balloon catheter of FIG. 17A in aninflated state in accordance with the present disclosure;

FIG. 18 illustrates an exemplary embodiment of an extending element inaccordance with the present disclosure;

FIG. 19 illustrates an exemplary embodiment of an extending portion in aretracted state after cell collection in accordance with the presentdisclosure;

FIG. 20 illustrates the separate extending portion of FIG. 19 in adeployed state in accordance with the present disclosure;

FIG. 21A illustrates a cross-sectional side view of an exemplaryembodiment of a ball tip everting balloon catheter prior to deploymentof the balloon in accordance with the present disclosure;

FIG. 21B illustrates a cross-sectional side view of an exemplaryembodiment of the ball tip everting balloon catheter of FIG. 21A in adeployed state in accordance with the present disclosure;

FIGS. 22A-22C illustrate an exemplary embodiment of an everting balloonexiting from a catheter in accordance with the present disclosure;

FIG. 23A illustrates a cross-sectional side view of an exemplaryembodiment of a balloon tip catheter in accordance with the presentdisclosure;

FIG. 23B illustrates the balloon tip catheter of FIG. 23A in accordancewith the present disclosure;

FIG. 23C illustrates the balloon tip catheter of FIG. 23A in accordancewith the present disclosure;

FIG. 24 illustrates a cross-sectional side view of an exemplaryembodiment of a balloon tip catheter in accordance with the presentdisclosure;

FIG. 25 illustrates a side view of an exemplary embodiment of a balloontip catheter in accordance with the present disclosure;

FIG. 26A illustrates a cross-sectional view of an exemplary embodimentof a handle of the catheter of FIG. 25 in accordance with the presentdisclosure;

FIG. 26B is a detail view illustrating an exemplary embodiment of a gearsystem in the handle portion of the catheter of FIG. 26A in accordancewith the present disclosure;

FIG. 26C illustrates a perspective view of an exemplary embodiment of alinear rack ratcheting assembly in accordance with the presentdisclosure;

FIG. 26D illustrates a side view of an exemplary embodiment of a dropkey-click of the linear rack ratcheting assembly of FIG. 26C inaccordance with the present disclosure;

FIG. 26E illustrates a side view of an exemplary embodiment of a gearjam in accordance with the present disclosure;

FIG. 27 illustrates a cross-sectional side view of an exemplaryembodiment of a balloon tip catheter in accordance with the presentdisclosure;

FIG. 28 illustrates a cross-sectional side view of an exemplaryembodiment of a balloon tip catheter in accordance with the presentdisclosure;

FIGS. 29A-29C are a series of side perspective views of an exemplaryembodiment of a steerable balloon tip using guide wires in accordancewith the present disclosure;

FIG. 30 illustrates a side perspective view of an exemplary embodimentof a balloon catheter and lead balloon tip in accordance with thepresent disclosure;

FIG. 31 illustrates a side perspective view of an exemplary embodimentof a balloon catheter with a flexible guide wire in accordance with thepresent disclosure;

FIG. 32 illustrates an exemplary embodiment of a balloon prior toinversion of the balloon into a catheter in accordance with the presentdisclosure;

FIG. 33 illustrates a cross-sectional side view of an exemplaryembodiment of a balloon tip catheter with a sheath and the balloon ofFIG. 32 inverted in accordance with the present disclosure;

FIG. 34A illustrates a side perspective view of an exemplary embodimentof a string filament with a series of printed indicia in accordance withthe present disclosure;

FIG. 34B illustrates a side perspective view of an exemplary embodimentof a string filament with a series of knots as indicia in accordancewith the present disclosure;

FIG. 35 illustrates an eversion of an exemplary embodiment of a balloonin accordance with the present disclosure;

FIG. 36A illustrates a cross sectional view of an exemplary embodimentof a balloon in accordance with the present disclosure; and

FIG. 36B illustrates a cross sectional view of an exemplary embodimentof a balloon in accordance with the present disclosure.

DETAILED DESCRIPTION

The present disclosure is not limited to the particular embodimentsdescribed herein. The terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting beyond the scope of the appended claims. Unless otherwisedefined, all technical terms used herein have the same meaning ascommonly understood by one of ordinary skill in the art to which thedisclosure belongs.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassedwithin the disclosure. The upper and lower limits of these smallerranges may independently be included or excluded in the range, and eachrange where either, neither or both limits are included in the smallerranges is also encompassed within the disclosure, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either or both ofthose included limits are also included in the disclosure.

As used herein, the singular forms “a,” “an,” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” or “includes” and/or “including” when used herein,specify the presence of stated features, regions, steps elements and/orcomponents, but do not preclude the presence or addition of one or moreother features, regions, integers, steps, operations, elements,components and/or groups thereof.

As described above, a challenge in effectively testing for early stagecancers (e.g., ovarian cancer) in women may include obtaining biopsysamples without undergoing a surgical procedure. Anatomically, theovaries are in close proximity to the fimbria at the region of thedistal opening or os of the Fallopian tube. Eggs released by the ovarymay be gathered by the fimbria and transported through the Fallopiantube to the uterus. With ovarian cancer, cells may be deposited in theFallopian tube, which may eventually migrate into the uterus. Cellsamples obtained from the uterus may detect ovarian malignancy; however,the incidence of migration of ovarian cancer cells into the uterus maybe too low to render uterine sampling a reliable diagnostic test forovarian malignancy.

A higher number of cancer cells may migrate to or originate in theFallopian tube, which may be concentrated in the distal portion of thetube, near the distal os. The ability to test cells in the Fallopiantube for malignancy may be of clinical value for the early detection andtreatment of such cancers. It is understood that early detectionscreening may be performed that detects migrating cancerous cells.

The Fallopian tube is extremely fragile and may be prone to perforationin a medical procedure. As such, safe introduction of a diagnosticdevice into the Fallopian tube may be difficult with known devices.Referring now to FIG. 1, a Fallopian tube 1 of a patient may extend froma proximal os 3 to a uterus, connecting at a uterotubal junction (UTJ)2, to a distal os 5 and connecting to ovaries 6. A perforation may occurat the UTJ 2, which is a constriction occurring distal to the proximalos 3 (e.g., opening) of the Fallopian tube. For example, in somepatients the UTJ 2 may be approximately 1 cm distal of the proximal os3. In some patients, the body lumen size at this constriction may be assmall as approximately 0.3 mm or 0.5 mm, while the body lumen size ofthe Fallopian tube adjacent to the UTJ may be approximately 1 mm.

According to exemplary embodiments, systems and methods of the presentdisclosure may engage an interior wall of a Fallopian tube and mayremove cells therefrom for diagnostic purposes. Devices and processesmay be provided for collecting such cells in a less invasive procedurethat in some embodiments occur without cutaneous incision. Although thedescription refers to sample collection and diagnostics of Fallopiantubes, it is understood that systems and methods of sample collectionand diagnostics may be applicable to any other body lumens, tubes, andducts, including but not limited to a bile duct, hepatic duct, cysticduct, pancreatic duct, lymphatic vessels, and circulatory vessels inaccordance with the present disclosure.

Embodiments of an exemplary catheter for Fallopian tube diagnostics maybe provided for the performance of less invasive procedures includingany of the following: (1) access to the proximal os of the Fallopiantube via an intrauterine approach; (2) advancement of an introducercatheter to cannulate and form a fluid tight seal with the proximal os;(3) use of a second catheter inside the introducer catheter to track thelength of the Fallopian tube out into the abdominal cavity; (4)inflation of a balloon at the end of the second catheter with retractionof the second catheter until the balloon seals the distal os of theFallopian tube (retraction of the second catheter may result in contactwith the intraluminal surface of the Fallopian tube to dislodge cellsfor improved sampling); and/or (5) irrigation of the Fallopian tube andrecovery of the irrigation fluid for cytology or cell analysis.

Exemplary embodiments of a catheter for Fallopian tube diagnostics forminimally invasive procedures may include any of the following: (1)access to the proximal os of the Fallopian tube via an intrauterineapproach; (2) advance of an introducer catheter to cannulate theproximal os; (3) use of a second catheter inside the introducer catheterto track inside the Fallopian tube. An inflated balloon at the end ofthe second catheter may be advanced across the proximal portion of theFallopian tube and may be everted further into the Fallopian tube; (4)the balloon may contact the intraluminal surface of the Fallopian tubeand may dislodge cells for sampling; and/or (5) the balloon may beremoved and inserted into a vial for cell collection and subsequentprocessing.

Embodiments of an exemplary catheter may be configured for insertioninto the Fallopian tube (see FIG. 1). The Fallopian tube has a curvature(e.g., having a tortuous pathway), and the soft tissue of the tube maybe collapsible, thereby resulting in multiple constrictions as passageis attempted. As described above, this may be particularly true at theuterotubal junction (UTJ), which may be muscular and therefore moreprone to perforation by insertion of medical instruments. In somepatients, the UTJ may also present a downward bend with a lumen size atthe constriction that may be as small as approximately 0.3 mm or 0.5 mm,while the body lumen size of the Fallopian tube adjacent to the UTJ maybe approximately 1 mm.

In at least one embodiment of the present disclosure, an elongatedballoon that is initially inverted into a catheter lumen may bedeployable. The balloon may partially evert to enter a proximal end ofthe Fallopian tube, e.g., the UTJ, thereby cannulating the proximal os.The balloon may evert upon pressurization of the balloon from inside thecatheter so that an unrolling mechanism of the eversion creates a paththrough the Fallopian tube regardless of tortuosity or constriction inthe Fallopian tube. In some embodiments, the balloon may evert by a pushwire advancement, which may be in concert with pressurization. A greatmajority of the length of the balloon may be substantially inelastic,such that the balloon does not substantially expand and dilate theFallopian tube as it everts. Balloon expansion may burst or otherwisedamage or injure the Fallopian tube. However, exemplary embodiments mayalso incorporate an elastic distal balloon end expandable to seal thedistal os upon retraction of the distal balloon. In embodiments, thedevice may have a balloon having a sufficient rigidity to cannulate theFallopian tube and sufficient flexibility for navigation through thetortuous path of the Fallopian tube to minimize potential damage orinjury. In some embodiments, the device may include support elements forcannulating the Fallopian tube so that the balloon may not collapse atthe proximal os.

Exemplary embodiments of systems and methods of the present disclosuremay include positioning, and deployment of, a distal end of a catheter.In some embodiments, a catheter distal end may be deliverable to aproximal end of the Fallopian tube by a hysteroscope. In someembodiments, the hysteroscope may be an exemplary hysteroscope (e.g.,FIG. 3). Regardless of the mode of deployment, a retracted portion of acatheter may be extendable to contact the interior wall of the Fallopiantube. It has been surprisingly found that the act of extending a portionof the catheter may remove a sufficient sampling of cells and/or tissuefrom the Fallopian tube wall to perform histological and/or cytologicalevaluation. For example, at least a portion of a length of the balloonmay contact the Fallopian tube for sample collection. In someembodiments, a majority of the length of the balloon may besubstantially inelastic such that the balloon does not substantiallyexpand and dilate the body lumen (e.g., Fallopian tube) as it everts. Insome embodiments, the balloon may be sized such that the body lumen doesnot expand or dilate as the balloon everts. As described above, balloonexpansion may burst or injure the subject's body lumen. According tosome embodiments and as discussed above with regard to the exemplaryballoon catheter, the balloon may be extendable by eversion from acatheter only longitudinally into the body lumen such that the balloondoes not substantially expand and dilate the lumen as the balloon evertsor is extended into the body lumen (e.g., the Fallopian tube). In someembodiments, the balloon may be extendable longitudinally into the bodylumen, where a diameter of an inflated balloon may be up toapproximately 10-15% greater than a diameter of a Fallopian tube. Radialexpansion of the balloon may be limited or controlled by the majority ofthe length of the balloon being substantially inelastic. It isappreciated that portions of a balloon that are not intended to beinserted within a lumen structure can be elastomeric and therefore maybe expandable in diameter and compliant rather than substantiallyinelastic. Such a hybrid balloon may be well-suited in embodiments whena seal is desired with the UTJ. Exemplary of situations when a seal isdesired may include irrigation of the lumen, filling the lumen with animaging contrast, diagnosing obstructions, and/or topical contact with atherapeutic agent, such as a chemotherapeutic or an antibiotic.

It has also been surprisingly found that withdrawal of an extendedportion of a balloon may remove still more cells. In some embodiments,the extended portion may be retracted prior to catheter removal so as topreclude dispersal of dislodged Fallopian tube cells to surroundingtissue. In some embodiments, a slidable sheath may be deployable toprotect the collected sample. Upon catheter removal the extended portionmay deposit at least a portion of the collected sample (e.g., luminalcells) via contact with a microscope slide or other diagnosticsubstrate, for testing for abnormal cells (e.g., cancerous cells). Insome embodiments, a dye may be releasable in the Fallopian tube foridentifying abnormal and potentially cancerous cells.

Referring now to FIGS. 2A-2D, an inverted inelastic sleeve 12 and anattached distal elastic balloon 14 may be insertable through anintroduction catheter 10 that may reside in the working channel 22 of anoperative hysteroscope 20 (FIG. 3), and used to cannulate the proximalos of the Fallopian tube 1, as shown in FIG. 2A. At FIG. 2B, the balloonmay be inflated to evert the sleeve 12 the length of the Fallopian tube1 and distend the distal elastic balloon 14. At FIG. 2C, the balloon maybe retracted proximally at least partially to seal the distal os 18 ofthe Fallopian tube 1, after full advancement of the inverted elasticsleeve 12 and inflation of the elastic balloon 14. FIG. 2D illustratesthe introduction of saline for irrigation along the length of theFallopian tube 1 between the introducer catheter 10 and the evertedsleeve 12. Retraction of the inflated elastic balloon 14 seals theopening of the distal os. Subsequent collection of the irrigation fluidobtains cell samples from substantially the entire length of theFallopian tube 1 for cell analysis in the detection of ovarian cancer orother medical conditions. In an embodiment, a dye may be present in theirrigation fluid that is introduced in the Fallopian tube foridentifying and/or differentiating abnormal and potentially cancerouscells. An illustrative example of a dye may include a fluorescentimaging agent attached to a modified type of folic acid, which may actas a homing device searching for ovarian cancer cells to attach onto. Insome embodiments, a multispectral fluorescent camera may illuminate thedetected cells, visually identifying their location, e.g., by a monitor.For ovarian cancer cells to grow and divide, the cells need largeamounts of the vitamin (folic acid). Special receptors on the surface ofthe cancer cells seize the vitamin, and whatever is attached to it, andpull it inside.

The catheter 10 described above, and in greater detail below may beintroduced into the uterus of a patient using an operating hysteroscope20, an example of which is shown in FIG. 3. An operating hysteroscope 20may include one or more working channels. One channel may provideirrigation to distend the uterus and allow endoscopic visualization, andone or more additional working channels 22 may allow instruments and/orcatheters to be advanced distally of the hysteroscope. A proximalintroducer catheter 10 (see, e.g., FIG. 2A and FIG. 4) may beadvanceable through a working channel of the operating hysteroscope 20,and may be used to cannulate the proximal os of a Fallopian tube. Aballoon 24 on the proximal introducer catheter 10 may be inflated toocclude the proximal os (e.g., FIG. 4), and the everting sleeve cathetermay be advanceable through the proximal introducer catheter 10 into theproximal portion of the Fallopian tube. The sleeve/balloon element 14may be fully everted, and the inflated balloon tip may be pulled back toseal the distal os. Irrigation may be introduced via a port 11, andaspirated via the irrigation port 11 on the proximal introducer catheter10, to collect the sample. Irrigation may also be introduced throughboth the everting sleeve catheter and the proximal introducer catheter,followed by aspiration through one or both ports (11, 13) of theproximal introducer catheter.

In embodiments of the catheter 10, the sleeve 12 of the everting sleevecatheter may be a flexible, elongated, substantially inelastic tube withan elastic balloon tip 14 attached to its distal end, see FIGS. 5A and5B. The inelastic tube 12 may have multiple ridges 15 disposed along itslength extending externally of the tube when the tube has been evertedor extended/deployed, such as illustrated in FIG. 5B. Prior todeployment, the ridges may extend inwardly, as the tube is inverted, asillustrated in FIG. 5A. With the ridges extending externally, as in FIG.5B, the ridges may be exposed to the luminal surface of the Fallopiantube when the sleeve is fully everted. These ridges may increase theability of the sleeve to gather cells upon balloon retraction, e.g., byadditional surface area, and/or frictional contact. In some embodiments,the outer surface of the everted inelastic balloon may be covered withfabric or otherwise textured, as described below, which may increasecell dislodgment and improve cell collection during balloon retraction.

FIGS. 6A-6C illustrate an exemplary embodiment of an everting sleevecatheter 10A which may provide protection of a bond between a balloon14A and a sleeve 17 of the everting sleeve catheter 10A duringdeployment. The everting sleeve catheter 10A of FIGS. 6A-6C may includean elongated, elastic balloon attachable to a distal tip of the evertingsleeve catheter. A substantially inelastic sleeve 17, slightly shorterin length than the elastic balloon 14, may be attached to the elasticballoon 14 at the distal tip of the catheter, and may be invertible sothat in an undeployed state, the inelastic sleeve 17 is positionedinside the elastic balloon 14. In response to eversion of theballoon/sleeve combination 14A, 17 the inelastic sleeve 17 may emergefrom a double wall 19 of the catheter 10A, so that a portion of theelastic balloon 14A in an extended position is internal to the inelasticsleeve 17, e.g., the inelastic sleeve 17 is disposed on the outside ofthe elastic balloon 14A and may constrict the elastic balloon 14A alongits length, e.g., a majority of its length, to prevent the elasticballoon 14 from expanding and potentially rupturing the Fallopian tubeduring the time that the everting sleeve is being advanced through theFallopian tube. Upon full balloon/sleeve eversion, the distal elasticballoon may inflate to approximately 3×-5× the diameter of the sleeve,for occlusion of the distal os upon retraction of the catheter withconcomitant pullback of the inflated balloon. In some embodiments, thecatheter may contain a port 11 to allow irrigation to occur between theballoon and the inelastic sleeve 17.

FIGS. 7A-7C illustrate an exemplary embodiment of an everting sleevecatheter 10 b including a concentric double walled catheter, and theeversion of three layers are attached to the distal catheter tip. Anelongated inelastic balloon 21 may be attached to a distal tip of theinner catheter 23, and the balloon 21 may lie within an inner catheterlumen 25. An elongated elastic balloon 14B, which in some embodimentsmay be equal in length to the inelastic balloon 21, may be attached to adistal tip of an outer wall 27 of catheter 10 b. The balloon 14B may bedisposed inside the inelastic balloon 21. An inelastic sleeve 29, whichin some embodiments may be shorter in length than the elastic balloon14B, may be attached to the distal tip of the outer catheter wall 27.The sleeve 29 may be disposed inside the elastic balloon 14B in anundeployed state. Pressurization of the inner catheter 23 may evert theinelastic balloon 21, which may deliver the elastic balloon 14B andouter inelastic sleeve 29. Following full eversion of all three layers,pressurization between the walls of the inner catheter and outercatheter may inflate the elastic balloon 14B. The inelastic sleeve 29may constrict the elastic balloon 14B along the majority of its length.A distal, un-constricted tip of the balloon 14T may expand to form theocclusion element. This may be advantageous to decrease friction in thesystem during the eversion process. For example, the inelastic balloon21 may deliver the elastic balloon 14B and inelastic sleeve 29. Theelastic balloon 14B may not undergo expansion until fully everted. Inthis manner, the elastic balloon 14B may avoid frictional contact withthe wall of the inelastic sleeve 29 during eversion, which may beadvantageous in facilitating deployment, e.g., when working with smalldiameter catheters for traversing the Fallopian tube.

FIGS. 8A-8B illustrate an exemplary embodiment of an everting sleevecatheter 10C including an inelastic sheath 29A having a small lumen 31for irrigation, with the sheath 29A connectable to a third port 11A usedfor fluid irrigation and aspiration to obtain cytology samples. As notedabove, in some embodiments, the irrigation fluid may contain a dye foridentification of abnormal and potentially cancerous cells.

Another exemplary embodiment according to the present disclosure isshown in FIGS. 9A-9C and 10A-10B. An elongated balloon 32 including anextending portion 34, e.g., an expandable member, attachable to a distalend of the balloon 32 may be inverted into the lumen 36 of a catheter30. In an inverted, e.g., undeployed state, the extending portion 34 maylie inside the elongated balloon 32. In some embodiments, the extendingportion 34 may be a spiral of one or more loops of filament 38. Thefilament that forms the extending portion 34 may be formed from avariety of materials illustratively including a monofilament polymermaterial such as Nylon or polypropylene, fluoropolymers, or polylacticacid; metal such as stainless steel titanium, or platinum; or asuperelastic metal such as Nitinol, or combinations thereof. In someembodiments a fiducial marker may be included on the filament and/orballoon and deliverable to the Fallopian tube (not shown) to facilitatesubsequent return to the situs of cell sampling. It may be appreciatedthat the extending portion may also have alternative configurations,such as an expandable member. The extending portion 34 e.g., expandablemember, may contain a plurality of outwardly oriented bristles 40 formedof polymer or metal (see FIG. 18). In some embodiments, the extendingportion 34 may be included as an elongated strand 38 of material thatcurls, spreads or fans out 42, balls up 44 to a predetermined shapedwhen released from being constrained inside the catheter (FIGS. 11A-11For FIGS. 14A-14B), or combinations thereof. In some embodiments, theextending portion 34, e.g., expandable member, may be formed of acompressed polymer foam that self-expands upon release into a wetenvironment (FIGS. 12A-12B). Upon pressurizing the catheter adjacent tothe proximal os, the balloon 32 may evert so as to urge the invertedportion outward into the extended position and into contact with theFallopian tube inner wall cells. In some embodiments, upon full ballooneversion, the extending portion 34 may be extended out of the distal osof the Fallopian tube and into the abdominal cavity. In someembodiments, the extending portion 34 may have an expanded outerdiameter of approximately 5-15 mm.

An advantage of the extending portion 34 having a plurality of bristlesis that there may be added surface area on which a sample (e.g., cellsand/or tissue) is collectable, including areas that are not likely to beexposed to shear forces when the device is retracted back within thecatheter. Cell collection may therefore be maximized, as well asminimizing an amount of cells that are wiped off when the device ispulled through the Fallopian tube or into a sheath, as seen in FIGS.18-20. In those embodiments in which the extending portion has a greatersurface area, the cell collection may increase per linear unit ofFallopian tube so engaged under like pressurization conditions, ascompared to a contourless extending portion.

In still other embodiments of a catheter in accordance with the presentdisclosure, the extending portion, e.g., expandable member, may form anynumber of shapes and contours. For example, multiple filaments 42 may beattached to the distal end of the balloon 32 that splay out upon ballooneversion to form a brush 42 (FIGS. 11A-11B). In some embodiments, abraided string or suture 43 may be extendable distally of the balloon 32upon eversion (see FIGS. 11C-11D), and in other embodiments, the braidedsuture may be formed of various materials and/or may be one or morecolors for visual confirmation of extension of the suture 43 (see FIGS.11E-11F). A polymer foam structure 46 may be compressed inside theballoon 32, and may self-expand in response to balloon 32 eversion andexposure to a fluid environment (FIGS. 12A-12B). An elastic or inelasticballoon 48 may be disposed on the distal end of the inelastic sleeveballoon 32 (FIGS. 13A-13B). Alternatively or additionally, embodimentsmay include an everting balloon having a superelastic wire coil (FIGS.14A-14B), a spiral everting balloon 50 (FIGS. 15A-15B), an evertingdistal arc balloon 52 (FIGS. 16A-16B), or a long elastic filament ofpolymer or metal that gathers into a three-dimensional structure uponballoon eversion, such as an inner lumen 54 (FIGS. 17A-17B), andexpandable member 34 having a plurality of outwardly oriented bristles40 (FIG. 18), or combinations thereof. It may be appreciated that any ofthese embodiments of a catheter extending portion as an expandablemember or otherwise may include a fiducial marker as a navigation aidfor a medical professional to navigate back to a desired situs in theFallopian tube. For example, a marker may be deliverable to a desiredlocation in a Fallopian tube, e.g., through an inner lumen 54, or by aballoon 32. Such markers are known to the art and illustratively includeradio-opacity markers, isotopic markers, and radiofrequency markers. Instill other embodiments, a biodegradable extending portion or apermanent extending portion may be severable from the catheter. In stillother embodiments, the extending portion may deliver a therapeutic agentsuch as a chemotherapeutic drug, antibiotic, anti-inflammatory, orcombinations thereof, of the Fallopian tube tissue.

When the catheter is retracted back into the working channel of thehysteroscope, cells may be dislodged from at least a portion of theentire length of the inner surface of the Fallopian tube. In someembodiments, the extending portion may be inverted back within theballoon by reducing the gas pressure within the balloon, and reinvertingthe balloon within the catheter tip region, so as to shield collectedcells with the catheter tip region internal bore. In other embodiments,the extending portion and balloon, in either a deflated state orremaining inflated, may be retractable back within a sheath without theballoon being reinverted. For example, as shown in FIG. 19, an extendingportion 34, e.g., an expandable filament 38 including a plurality ofbristles 40, may be protected during removal from the patient by asheath 162 (see FIG. 23A).

An extending portion 34, e.g., an expandable filament 38 as shown inFIGS. 18-20, may be attached to an end of the inverting balloon. In someembodiments, an extending portion 34, e.g., expandable coil, may beconnected to the push wire (see FIG. 23A). In some embodiments, theextending portion may be connected to a distal end of the push wire 134.In some embodiments, an extending portion 34 (e.g., spiral) may be acollection device passed through an inner lumen that may expand uponreaching the distal end into the Fallopian tube. It may be appreciatedthat cells may be collectable from a specific portion of the Fallopiantubes, for example the fimbria, and then protected by a sheath 162 so asto minimize potential for distal cells to be wiped off by the innersurface of the proximal Fallopian tube as the device is removed.

In some embodiments, friction between an outer surface of the extendingportion 34, e.g., an expandable filament 38, and an inner lining of theFallopian tube is sufficient to dislodge cells and adhere such cells tothe expandable member, even in embodiments having a contourlessextending portion. For example, an expanded spiral at the distal end ofthe balloon may contact the fimbria at the distal end of the Fallopiantube to collect cell samples. Since the Fallopian tube increases ininner diameter as it proceeds from its proximal to its distal end,expansion of the extending portion 34, (e.g., by the expandable filament38) may maximize obtained cell samples at the distal end of theFallopian tube (e.g., fimbrial portion of the Fallopian tube).

The elongated balloon and the extended portion may in some embodimentsbe retractable into the working channel of the hysteroscope to avoidloss of cell samples as the hysteroscope is removed from the patient. Anelastomer seal at the proximal end of the working channel of thehysteroscope may seal against an outer surface of the catheter. Thisseal may act to deter the catheter from sliding from a desired positionwithin the working channel of the hysteroscope, or from slidingcompletely out of the working channel. A mark on the catheter body mayindicate a length of retraction necessary to ensure that the elongatedballoon and distal spiral are fully within the hysteroscope workingchannel. Upon removal of the hysteroscope from the patient, in someembodiments, a syringe containing saline solution may be attached to theLuer fitting at a proximal end of the working channel. Saline may beused to flush cells gathered by the elongated balloon and expandingspiral into a test tube. It may be appreciated that the cells collectedby the expandable member may be collected for testing by conventionaltechniques and may be prepared for cytological, molecular or geneticexamination.

In some embodiments, an inner lumen 54 may be formed of a materialhaving sufficient rigidity to maintain an opening in the lumen. Forexample, the inner lumen 54 may be sufficiently rigid to withstand apressure of the balloon as it is inflated and everted. In embodiments,the inner lumen 54 may be formed of a metal, composite, or polymer, orcombinations thereof, including a polyethylene terephthalate (PET)material and may be attached to the catheter, as shown in FIGS. 17A-17B.The eversion process follows that of the aforementioned embodimentshaving a push wire that does not include a lumen. This embodiment mayalso include an inflation sideport and a proximal seal 33 that may allowthe balloon 32 to be everted while maintaining an orifice through theinner lumen 54 in fluid communication between the hysteroscope and thepatient body tissue. Once everted, the inner lumen 54 may provide apathway through which a separate extending portion may be passed, or asurgical instrument package or visualization device may be passed. Insome embodiments, various agents may be brought into contact with thelumen via the pathway. These agents and rationales therefore mayillustratively include microbubbles to serve as acoustic contrastagents, contrast dyes for various forms of spectroscopic imaging, ortherapeutics for treating cells or killing cancerous cells, orcombinations thereof. Therapeutics may illustratively include antibodiesspecific to cancerous cells and carrying a chemotherapeutic orradio-isotope, chemotherapeutics, radio-isotopic seeds, antibiotics,antifungals, or combinations thereof.

FIGS. 21A-21B illustrate cross-sectional views of an exemplaryembodiment of a ball tip everting balloon catheter 120 in accordancewith the present disclosure. A spherical ball 122 may be attached to thedistal end of a spring tip 124 affixed to a tube, or catheter 126. It isunderstood that “tube” and “catheter” 126 may be used interchangeably.The spherical ball 122 may be provided to negotiate through a patient'sUTJ to minimize and/or avoid inadvertent penetration through the UTJsidewalls. The spring tip 124 may allow the distal end with the ball 122to flex around corners and navigate through the UTJ. The spring tip 124and spherical ball 122 may have an open lumen 128 extendable through thespring tip 124 and the spherical ball 122. The spherical ball 122 on thespring tip 124 may be approximately 0.8-1.0 mm in diameter, and thehollow spring tip 124 may have a length of approximately 1.5 cm and anouter diameter of approximately 0.6 mm. The hollow spring tip 124 may beformed of a metal (stainless steel or superelastic metal, e.g., Nitinol)coil spring sheathed on the outside with thin walled polymer heat shrinktubing, made of nylon, PET (polyethylene terephthalate), or similarmaterial. In some embodiments, the spring tip 124 may be a metal coilspring co-extruded into a tubular polymer body. The hollow spring tip124 may also be a flexible polymer tube, and in some embodiments may bemade of nylon, Polyethylene terephthalate (PET), polyether block amide,or similar materials. An everting balloon 130 may lie inside the hollowspring tip 124. The everting balloon 130 may extend proximally insidethe main lumen 132 of the introduction catheter 126 (e.g., a generallyflexible tubular structure) or cannula (e.g., a generally rigid tubularstructure).

The proximal end of the everting balloon 130 may be attached to a pushrod 134 passable through a seal 135 on the proximal end of the catheter126 or cannula. In operational use on a patient, the flexible ball tip122 may be manually advanced through the UTJ. Once passage of theflexible ball tip 122 and spring tip 124 through the UTJ occurs, thepush rod 134 may be advanced through the seal 135 of the previouslypressurized introduction catheter 126 or cannula. Advancement of thepush rod 134 may cause a controlled eversion of the balloon 130 out ofthe hollow spring tip 124, through the length of the Fallopian tube.

According to some embodiments, a seal 137 may be disposed within thetube/catheter shaft 126 through which the push wire 134 passes as thepush wire 134 actuates the balloon (see FIGS. 21B, 23A). In someembodiments, the seal 137 may be a conical seal disposed between apressurized chamber 116 and the push wire 134. It is noted that theterms “push wire” and “push rod” are used herein synonymously. Theconical seal 137 may allow the push wire 134 to advance through thecatheter 126 to actuate the balloon 130 between an inverted position andan everted position while maintaining pressure in the catheter 126.Various embodiments of the present disclosure may provide an adjustableseal 135, disposed proximal to the conical seal 137. In response to aleak forming between the push wire 134 and the conical seal 137, theadjustable seal 135 may be adjusted to maintain the pressure required tomove the balloon between the first inverted position and the secondeverted position. The adjustable seal 135 may be a rotating hemostasisvalve, e.g., a device for maintaining seals between coaxial devices, andadjustable by knob 133. In some embodiments, a hemostasis valve may beused as seal 135. The hemostasis valve may include a compressible gasketto provide a desired degree of sealing.

The knob 133 may be rotatably adjustable to adjust the seal 135. In use,a user may be able to adjust the knob 133 to tighten or loosen the knob133. By tightening the knob 133, the seal 135 may be compressed, therebycollapsing around the push wire 134. The rotatable knob 133 may providethe user with improved control over the seal and the ability to react ifthere are any leaks from the conical seal 137.

In embodiments, the elongated balloon may be initially inverted into acatheter lumen during assembly, e.g., the balloon may be turned insideout during assembly. The balloon may be pressurized to deploy, so thatthe balloon everts and “unrolls” into the Fallopian tube. The unrollingmechanism of the eversion may track through the Fallopian tuberegardless of tortuosity or constriction in the Fallopian tube. A greatmajority of the length of the balloon may be substantially inelastic,e.g., up to 100% of the length of the balloon, such that the balloon maynot substantially expand and dilate as it everts, e.g., so the Fallopiantube may not expand or dilate as the balloon everts. In otherembodiments, a portion of a distal end of a balloon may be expandableinto the fimbriated end of the Fallopian tube (e.g., see FIGS. 5-8).Balloon overexpansion may burst or injure the Fallopian tube.

An exemplary process common to the various embodiments of devices mayinclude the deployment of the distal end of a catheter. In someembodiments, a catheter distal end may be delivered to a proximal end ofthe Fallopian tube by a conventional hysteroscope. Regardless of themode of deployment, a retracted portion of the balloon inside of thecatheter shaft 126 may be extendable from within the catheter shaft 126into contact with an interior wall of the Fallopian tube. It has beensurprisingly found that the act of extending the portion may abrade asufficient amount of cells and/or tissue from the Fallopian tube wall toperform histological evaluation. This is observed for planar surfaces ofa balloon of seemingly non-abrasive character. While a roughened surfacetexture on the balloon may be included for contacting the Fallopian tubewall in some embodiments, the surface of the inelastic balloon portionmay be sufficient to dislodge a sufficient amount of cells and/or tissuefor statistically meaningful histological evaluation regardless ofwhether the balloon is fully inflated or partially deflated andcrinkled. It has also been surprisingly found that withdrawal of theextended portion may removes still more cells. In other embodiments, theextended portion may be retracted prior to catheter removal so as topreclude dispersal of dislodged Fallopian tube cells to surroundingtissue. Upon catheter removal, contacting the exposed portion of theextended portion, now covered in cells with a microscope slide or otherdiagnostic substrate, may be sufficient to test for abnormal cells andin particular cancerous cells.

The catheter 126 described above, and in greater detail below may beintroduced into the uterus of a patient using an operating hysteroscope20, an example of which is shown in FIG. 3. An operating hysteroscope 20may include one or more working channels. One working channel mayprovide irrigation to distend the uterus and allow endoscopicvisualization, and one or more additional working channels may allowinstruments and/or catheters to be advanceable distally of thehysteroscope. The catheter 126 (e.g., FIGS. 21A and 21B) may beadvanceable through the working channel of the operating hysteroscope,and may cannulate the proximal os of a Fallopian tube. The evertingballoon 130 may be advanced through the proximal catheter 126 into theproximal portion of the Fallopian tube.

FIGS. 22A-22C illustrate an exemplary embodiment of an everting balloon130 exiting from a flexible tip 152 with a spherical ball 122 inaccordance with an embodiment of the disclosure. The nylon flexible tip152 and spherical ball 122 may be configured to pass through the patientUTJ for the deployment of the everted balloon 130 in the Fallopian tube.In an embodiment, a ball tip everting balloon catheter 150 may beconfigured with approximately a 0.9 mm ball tip on approximately 0.66 mmdia.×18 mm long tip. In some embodiments, the tip may be formed ofnylon. In some embodiments, a 4 Fr catheter with a 0.64 mm diameterballoon that may evert through and beyond the tip.

FIGS. 23A-23B illustrate a cross-sectional side view of a balloon tipcatheter, or device, 160 in accordance with the present disclosure. Insome embodiments, a balloon 130 may have an outer diameter ofapproximately 0.8-1.0 mm, and may have an initial everted length ofapproximately 1-3 cm, e.g., approximately 1.2-1.5 cm extending out ofthe distal end of the catheter 126 or cannula. The balloon 130 may befully evertible into the Fallopian tube, e.g., extending approximately7-12 cm. The balloon 130 may be securable to a distal end of thecatheter shaft or tube 126, as indicated at reference numeral 117, and apush wire 134, as indicated at reference numeral 118. For example, thedistal end 118 of the push wire 134 may form an end of the balloon 130.In embodiments, the balloon 130 may be bonded to the distal end 118 ofthe push wire 134. The push rod or wire 134 may actuate the balloon 130from an inverted position in the catheter 126 to an everted positionwhen an interior of the balloon, between the catheter 126 and theballoon 130 and indicated by reference numeral 119, is pressurized. Inembodiments, an everted position may include at least a portion of theballoon 130 extending beyond the distal end of the tube 126. In someembodiments, the balloon 130 may be initially partially everted andfixed to the catheter 126, forming a rounded end 130 a. In someembodiments, the balloon 130 may be inflatable with fluid to a pressureof approximately 14-24 atm (206-353 psi).

In some embodiments, as described above, the device 160 may include asheath 162. The sheath 162 may be coaxial with the catheter 126. Thesheath 162 may be slidably adjustable relative to the catheter 126 tocover at least a first length of the balloon 130 extending outward fromthe distal end of the tube 126 in an everted position. The sheath 162may form a physical barrier between the balloon 130 and the interior ofthe scope to protect the balloon. For example, an initial length, e.g.,approximately 1.5 cm of the balloon 130, may be extended from thecatheter 126 during insertion through the scope. As the balloon isactuated (e.g., via the push wire 134 and/or balloon pressurization),the sheath 162 may protect the balloon in at least one of the invertedposition, a partially everted position, or a fully everted position, orcombinations thereof.

The sheath may also act to provide column strength to the balloon as itis everted. In some embodiments, a portion of the sheath 162 may be atleast partially translucent, optically transparent, or combinationsthereof, as indicated at reference numeral 162 a. In embodiments, thetransparent portion 162 a of the sheath 162 may at least partiallyoverlap with a transparent portion 167 of the catheter 126. For example,a medical professional may be able to visualize the balloon 130 (e.g.,to confirm positioning and/or full balloon extension) with thehysteroscope 20 through at least a portion of the sheath 162 and/or thecatheter 126. In some embodiments, the catheter may include a sheathknob 164 located at a proximal end of the sheath 162 to connect thesheath 162 to the tube 126.

The pressurized balloon 130 may have a rounded end 130 a for atraumaticcannulation of the proximal os and advancement within the Fallopian tubeand a degree of flexibility along the balloon 130 length. The balloon130 may have sufficient column strength to allow the balloon 130 to bemanually advanced through the UTJ, for example, with a push wire 134,under at least a partial pressure or no pressure. In some embodiments,the balloon 130 may be constructed of a thin-walled polymer material,such as polyethylene terephthalate (PET), polyethylene, Nylon, polymer,or a similar material. The balloon 130 may have a wall thickness fromapproximately 0.0001 to 0.001 inches and in some embodiments betweenapproximately 0.00019 and 0.00031 inches. In some embodiments, theballoon 130 may have a thickness of less than 0.005 inches. The materialand/or thickness of the balloon may be important characteristics of theballoon impacting how the balloon acts as it is deployed and withrespect to cell collection. For example, too thin of a balloon wall mayresult in the balloon lacking sufficient column strength (acting morecompliant or elastic as desired), or too thick of a balloon wall mayresult in the balloon resisting everting or everting in an inconsistentmanner. The thickness of the material may affect the contouring,wrinkling of the balloon surface to the extent the surface features arecreated or enhanced by the act of inverting, when loading the balloon inthe catheter, which in turn may affect the ability to collect and retaincells. The material of the balloon may also impact whether the balloonmay adhere or tend to stick to itself during eversion or after beingdeflated and withdrawn with the catheter.

In some embodiments, a first marker 171 may be disposed on at least aportion of catheter 126. The first marker 171 may be a preparationmarker, indicating a desired position of the sheath knob 164. When thesheath knob is aligned with the first marker 171, the proximal end ofthe sheath 162 may be a reference point for the medical professional forballoon extension during preparation and initial cannulation of theballoon 130 into the Fallopian tube. In embodiments, at least a portionof the catheter 126, e.g., a proximal portion connected to thetransparent portion 167, may be formed of a metal such as stainlesssteel, or other materials such as composites, or polymers, orcombinations thereof. The first marker 171 may indicate to a user anappropriate location of male luer lock fitting, or sheath knob, 164 withrespect to the balloon 130 within the sheath 162, so that the sheath 162may be extended distally an initial length as a preparation step tocover, for example, approximately 10 to 20 mm length of everted balloon130 that is used to access the proximal os before the balloon iscompletely everted.

When in position at the proximal os, the sheath may be pulled back fromthe first marker 171 to the original position, exposing the partiallyeverted balloon tip for accessing and placement in the Fallopian tube.In embodiments, the sheath 162 may be extendable along a longitudinalaxis to a point beyond the distal end of the catheter 126. When thesheath 162 is extended distally of the catheter 126, a distal tip of thesheath 162 may be an indicator for balloon advancement. The first marker171 may include a score line, a coating substance, or a selectivelyoxidized region. In some embodiments, the first marker 171 may be anopaque band of material (e.g., including but not limited to polymer, ormetal, or combinations thereof) attachable to at least a portion of thecatheter 126 (e.g., metal portion, or hypotube 138) using, for example,an adhesive, bonding, or welding process. Such a preparation marker mayallow the medical professional to know how far to deploy the balloon 130in the initial preparation step, thereby improving the ease of use ofthe device by eliminating the need for an outside measuring tool andimproving the safety of the procedure by eliminating any guesswork oreyeballing on the part of the user.

In some embodiments markers may be incrementally spaced apart in knownpredetermined distances from each other such that a medical professionalmay use the markers as a visual counter or measuring device to verify anapproximate length of balloon that has been everted. It is appreciatedthat any inner cannula or catheter described herein may include indiciaas described for assistance in navigating patient anatomy.

In some embodiments, a second marker 173 may be disposed on the catheter126, e.g., a metal portion 138, to indicate a desired location of sheathknob 164 to confirm that the sheath 162 covers the deployed evertingportion (balloon, suture, etc.) during device removal into thehysteroscope 20. For example, the second marker 173 may be a retractionmarker. This may allow the user to visualize and confirm that theballoon 130 is fully protected by the sheath 162 during the removalprocess to avoid loss of cells collected on the balloon and/or extendedportion. When the hysteroscopic view is obscured, for example, by bloodor tissue in the distension fluid, additional user visualization by thesecond marker 173 may be advantageous. The second marker 173 may beformed by the same techniques used to form the first marker 171. Thesecond marker 173 may also be included on any inner cannula or catheterdescribed herein.

In some embodiments, a portion 167 of the catheter 126 and/or distalportion of sheath 162 may have a transparent section along its length ora portion that is translucent, optically transparent, or a combinationthereof under use conditions. According to embodiments of the presentdisclosure, the tube or catheter 126 may include at least one visualmarker. In other embodiments, the visual marker on the catheter 126 maycomprise a third marker 179 disposed on the catheter 126. The thirdmarker 179 may be located near or at the distal end of the catheter 126shaft where the balloon 130 is connected to the catheter 126. In someembodiments, the third marker 179 may be radio opaque. The third marker179 may visually indicate to a user the end of the catheter 126 shaft,thereby improving control of the catheter 126. The ability to visualizethe end of the catheter 126 may be desirable during cannulation, whenthe balloon 130 is advanced beyond sheath 162 into the Fallopian tube.The third marker 179 may allow a user to visualize the distal end of thecatheter 126 as the cannulation step progresses. The user may be able tosee when the cannulation step is complete, e.g., when the third marker179 aligns with the end of the sheath 162 at the os, thereby improvingease of use. The third marker 179 may be formed by the same techniquesused to form the first marker 171 and/or the second marker 173. Thethird marker 179 may be provided in an easy to see color, for exampleblack or blue.

In some embodiments, a string, braid, and/or suture 121 may beextendable distally of the balloon 130 as the balloon 130 everts in theform of an extendable portion of the balloon 130. In some embodiments,the string or suture may be attached to the distal end of the push rodor to the balloon tip, by bonding or adhesive, e.g., at referencenumeral 118. In an inverted position of the balloon 130, the string,braid, and/or suture 121 may be positioned internal to the balloon 130,e.g., within the tube of the catheter 126 as shown in FIG. 23A. Uponeversion of the balloon 130, e.g., by actuation of the push rod, thestring, braid, and/or suture may extend to a position that becomes theexterior to the balloon, either extending distally from the distal tipof the balloon 130, or extending proximally from the balloon tipalongside the exterior of the balloon.

In some embodiments, at least a portion of the string, braid, and/orsuture 121, e.g., as indicated by reference numeral 43 in FIGS. 11C-11D,may be braided. The braided string or suture 43, 121 may comprise one ormore filaments. The string or suture 43, 121 may be extendable when theballoon 32, 130 is everted. In some embodiments, the string or suture43, 121 may be a plurality of braids. In some embodiments, the string orsuture 43, 121 may be formed of one or more colors, e.g., to improvevisualization for the medical professional to confirm that the balloonis everting properly (see FIGS. 11E-11F). For example, the colors may bevisualized through the scope as the balloon is everted and the string orsuture 43, 121 is pushed out with balloon. Since the balloon 32, 130 iseverting, the string or suture 43, 121 within the interior of theballoon 32, 130 may advance out of the balloon at approximately twicethe distance as the balloon everts (e.g., as the balloon everts 1 mm,approximately 2 mm of string or suture is exposed beyond the distal endof the inner cannula/tube. The colors may determine positioning of thesuture or string 43, 121 in the Fallopian tube for sample collection. Insome embodiments, the string or suture 43, 121 may include one or moreregions having printed indicia, or color variations along the lengththereof, or combinations thereof. In some embodiments, the string orsuture 43, 121 may include one more knots along its length inpredetermined spaced known increments to provide further visual ortactile feedback to the medical professional (see FIGS. 34A-34B). Thecolors and/or knots may be placed at incremental distances from eachother, so that a count of the colors or knots may be translated to anapproximate amount of distance/length that the suture or string 43, 121(and to some extent the length of the balloon 130) has been everted.

In some embodiments, the balloon material may be treated to change thesurface properties of an exterior surface of the balloon 130. Processessuch as plasma or corona treatment may increase surface receptiveness tovarious substances that illustratively include subject cells, inks,coatings, adhesives, laminates, and paints, or combinations thereof.Surface treatment may enhance wettability creating a surface withhydrophilic properties, or discourage wetting creating a surface withhydrophobic properties. Surface treatment may be used to improve theadhesion properties of the balloon surface, to create a surface in whichcells are more likely to adhere compared to an untreated surface.

Surface treatments may also be used to prepare the balloon surface forprinting indicia on the surface, e.g., including PAD printing. PADprinting (also called tampography) is a printing process that maytransfer a 2-D image onto a 3-D object. Indicia printed on the balloonsurface may serve as preparation markers for the user. These preparationmarkers may allow the user to know the length of the balloon 130 priorto deployment of the balloon 130, thereby improving the ease of use ofthe device by eliminating the need for an outside measuring tool andimproving the safety of the procedure by eliminating any guesswork oreyeballing on the part of the user.

In addition to marking for visualization purposes, the balloon 130 mayalso be treated with a process that increases surface area such as theapplication of a nanofiber or micropillar surface (e.g., including butnot limited to ULTRA-WEB® from Corning), which may improve cellcollection yield and/or retention compared to a balloon with little orno surface treatment. The suture or string 121 may include similarsurface treatment features as a way to enhance cell collection andretention.

In various embodiments, the balloon 130 may be formed of a material suchthat the balloon 130 is capable of moving between the inverted andeverted positions without excessive deployment pressures, yet rigidenough so that the balloon does not excessively radially expand duringeversion. The material may also allow for wrinkles, overlappingmaterial, or micro ridges, or a combination thereof to be formed on theballoon surface during manufacturing and/or assembly, for example bypolymer deformation. Such wrinkles, overlapping material, ormicro-ridges may be created on a normally smooth (contourless) balloonsurface material, or may enhance a balloon surface material that alreadyincludes one or more surface features. The wrinkles, overlappingmaterial, or micro ridges formed in the balloon material may remainduring balloon eversion and/or inversion, e.g., the balloon surface maybe plastically deformed. Wrinkles, overlapping material, and/or microridges may improve cell collection of the balloon 130. For example,cells may be removed from the Fallopian tube during balloon eversionand/or may be captured within the wrinkles as the balloon 130, so thatwhen the balloon 130 is retracted into the sheath 162 and the catheter126 is removed with the scope, cells may be retained within the wrinklesof the balloon 130. Relieving pressure in the balloon, to deflate orpartially deflate the balloon, prior to retraction, may act to increaseor reform wrinkling on the balloon surface and further improve cellcollection and/or retention. In some embodiments, the surface of theballoon 130 may be roughened, or otherwise adjusted, to increase asurface area. According to various embodiments, the balloon may be madeof polyethylene terephthalate (PET), polyethylene, nylon, afluoropolymer, or a perfluoropolymer, or other similar suitablematerial.

In some embodiments, a surface area of the balloon 130, e.g., thesurface for contacting the inner surface of the body lumen (Fallopiantube) may include additional surface features. In some embodiments, aballoon surface that is relatively smooth because of the materialcharacteristics may be modified to include wrinkling and added surfacearea, e.g., by processes employed during manufacture or packaging thatimpart surface features to the balloon surface that are retained duringuse of the device. In other embodiments, a balloon material surface thatis maintained relatively free of any contouring, may still be able tocollect and retain cells just through the mechanism of everting andengaging the tissue lumen with the balloon and then (optionallydeflating and) retracting the balloon along the tissue wall, asdescribed above. In some embodiments, a surface of the balloon 130 maybe embossed to impart micro ridges having peak-to-valley heights of fromapproximately 0.1 to 500 microns through a variety of conventionaltechniques that illustratively include plate-to-plate, roll-to-plate androll-to-roll. In some embodiments, the peaks and valleys may beconfigured to be large enough to provide additional surface area butsmall enough to minimize the potential of peaks and valleys lockingtogether. For example, peaks and valleys in the balloon surface area mayinterlock during inversion/eversion such that balloon movement may beimpeded. It may therefore be advantageous to configure the peaks andvalleys to have a profile to minimize potential interlock.

In some embodiments, a polymer surface of the balloon 130 may be etched.Etching may be accomplished by a variety of conventional techniquesincluding but not limited to solvent, chemical, laser, or plasmaexposure. Etching may be advantageous to increase a surface area withoutincurring the stressing on the balloon of having embossing tool contact.This feature may improve cell collection of the balloon by increasingsurface area and creating micro-edges that are normal to the axis of theballoon as it is removed. In some embodiments, as above, polymers havinglow surface energies and/or having a limited ability to crinkle/wrinkleat any balloon thickness upon embossing and/or etching are nonethelessoperative herein for cell biopsy as the opposing contacting surfaceshave sufficient glide to allow the balloon to evert smoothly, whilehaving enough surface area to dislodge and retain cells. Low surfaceenergy polymers in embossed or etched form may include fluoropolymers,perfluoropolymers, polyalkylenes, polypyromellitimide (Kapton H), orpolystyrene, or combinations thereof.

In some embodiments, etching or embossing may be formed on a balloonsurface in concentrated portions of the balloon, e.g., as indicia. Forexample, balloon markings may provide a visual indication for themedical professional to determine an extension of the balloon into theFallopian tube. Concentrated etchings and/or embossing may be visible bythe medical professional, e.g., potentially eliminating a need for aseparately attached marker or other indicia. A marker formed as aportion of the balloon may be advantageous to minimize and/or avoidpotential detachment.

The balloon 130 may be translucent, optically transparent, or acombination thereof. In some embodiments, the balloon 130 may be atleast partially opaque to enhance visibility during use. In someembodiments an opaque fluid may be mixed in the inflation fluid tocontrol color of the balloon and to further enhance visibility of theballoon. The amount of the opaque fluid added to the inflation fluid maycontrol the level of translucence or opacity of the balloon. In someembodiments, the fluid may be rendered opaque or otherwise detectablethrough the inclusion of colloidal or suspended particulate ormicrobubbles released within the fluid. Colloidal or suspendedparticulate operative herein include without limitation,polymethylmethacrylate, mica, barium sulfate, starch, and combinationsthereof.

The length of the fully everted balloon 130 may extend to approximately7-12 cm within the lumen (e.g., Fallopian tube), such that when fullyeverted, the balloon 130 may extend within the patient's Fallopian tube,following the successful advancement of at least a portion of length ofeverted balloon through the UTJ. Eversion of the balloon 130 may beperformed in a controlled manner, e.g., by advancing a push rod 134through a fluid tight seal 135, at the proximal end of the catheter 126.As described above, at least a portion 167 of the catheter 126 may betransparent or translucent, so that movement of the balloon 130 may beviewable through the hysteroscope through which the catheter 126 isinserted, thereby providing the user with a direct view of the insertionprocedure. The catheter 126 may be constructed of polymers such asNylon, polyether block amide, polyurethane, PET (polyethyleneterephthalate), polyethylene, or polyvinyl chloride (PVC), with orwithout polymer or metal coil or braid reinforcement, or combinationsthereof.

In some embodiments, the transparent or translucent portion 167 of thecatheter 126 may be at least approximately 1 cm in length forvisualization of the balloon deployment through the hysteroscope view.Providing a transparent or translucent portion 167 that is of anadequate length may ensure visualization of the balloon deployment whileproviding sufficient catheter column strength for Fallopian tubecannulation. In embodiments, the transparent portion 167 of the catheter126 may have a length relative to an opaque portion, e.g., a metalhypotube portion 138, to balance desired column strength and support tothe catheter 126 with visualization at the distal end. In someembodiments, the transparent portion 167 may extend to a proximal end ofthe device, within the metal portion 138. It is understood thatmaterials used to form the transparent portion 167 of the catheter 126may have lower column strength than a metal hypotube portion 138. Thisbalance may improve ease of use (e.g., by visualization of the distalend) and control of the device (e.g., by having sufficient stiffness toenable placement of the device at the ostium of the Fallopian tube andmaintain position throughout the procedure).

In some embodiments, a balloon 130, when everted at least partially outof the catheter 126 or cannula, may not remain straight. Rather, theballoon 130 may assume an undesired curved configuration, either asingle “C” curve, or an “S” curve, that may be difficult to use tocannulate the proximal os of the Fallopian tube, and to advance theballoon through the UTJ. The extended length of everted balloon 130 maybe straightened out or maintained straight by use of an outer sheath 162that lies coaxial about the exterior of catheter 126 or cannula, and mayassist in providing column strength and cover of the partially evertedballoon tip. At least a portion of sheath 162 and/or catheter 126 may betransparent 167, e.g., 167 of FIG. 23A, so that movement of the balloon130 may be viewable through the hysteroscope through which the catheteris inserted, thereby providing a user with a direct view of theinsertion process. Similar to catheter 126, the sheath 162 may beconstructed of polymers such as Nylon, polyether block amide,polyurethane, PET (polyethylene terephthalate), polyethylene, orpolyvinyl chloride (PVC), with or without polymer or metal coil or braidreinforcement, or combinations thereof. The sheath may be alignable withrespect to the catheter and/or the balloon, thereby providing columnstrength to the balloon. In response to cannulation of the balloonthrough the UTJ into the Fallopian tube, the sheath may support theballoon from outside of the proximal to minimize and/or prevent collapseas the balloon is further everted after navigating the UTJ. The sheath162 may also protect the sample (e.g., cells) collected on the balloonand/or extended portion. For example, the sheath 162 may protect theballoon in an everted position after contacting an inner surface of theFallopian tube. In some embodiments, the sheath 162 and balloon with orwithout extended portion may be retracted coaxially with the inner lumenof the sheath to extend the sheath over the everted balloon, andextended portion, if included, subsequent to cell collection. In someembodiments, the sheath 162 may remain stationary relative to theballoon 130 and/or the catheter 126, so that the balloon 130 is receivedin the sheath 162 subsequent to cell collection. As the balloon 130 iswithdrawn into the sheath and removed from the patient, the sheath mayprotect the cells to minimize and/or prevent loss of the samplecollection by providing a barrier from distention fluid in the uterus orirrigation fluid in the Fallopian tube or uterus. For example, theballoon subsequent to cell collection may otherwise be exposed toenvironmental conditions that may render the sample collection unusable,and/or otherwise wash the cells from the balloon and extended portion.

FIG. 35 illustrates an exemplary embodiment of a linear eversion of aballoon 130 in accordance with the present disclosure. In embodiments,one end of the balloon may be fixed to inner cannula/tube at point X(e.g., reference numeral 117 as illustrated in FIG. 23A) and the otherend of the balloon may be movable at point Y (e.g., reference numeral118 as illustrated in FIG. 23A). The balloon 130 may evert from theposition shown in Step 1 to the position shown in Step 2 to the positionshown in Step 3. In the eversion process, points A, B, and C movetowards the left side of the diagram, e.g., extend distal of the distalend of the device 160. As the balloon 130 unrolls/everts at/toward theleft side of the diagram, point A may move from the inside surface ofthe balloon to the outside surface. In practice, the balloon 130 thathas been partially, or initially, everted during the preparation stepmay be advanced further into the proximal end of the Fallopian tube.Further eversion (extension) of the balloon (in total up to the fulllength of the Fallopian tube, approximately 7-12 cm) may be accomplishedby further rotation of a drive wheel 204 (see FIG. 25). The balloon 130may then be deflated by relieving pressure in the inflation device. Theballoon 130 may then be retracted from the Fallopian tube. Because theFallopian tube is a potential space, the Fallopian tube tissue may tendto collapse around the balloon. Because the balloon fills the Fallopiantube, the balloon surface area may be substantially equivalent to thesurface area inside the Fallopian tube. This surface area may optimizetissue collection from the inside of the Fallopian tube. While deflationof the balloon may be desirable prior to retraction, it may be possiblein some embodiments to retract a balloon/extended portion from aFallopian tube without first deflating the balloon and still retainingcells collected thereon. For example, the balloon 130 in an inflatedand/or a deflated state may be retracted within the sheath 162 whileretaining a sufficient amount of cells on the surface of the balloon 130for testing. Alternatively, the balloon may be repeatedly inflated anddeflated while extended in the Fallopian tube, so that each time theballoon contacts Fallopian tube walls, more cells may be collectedand/or retained by the balloon.

As mentioned, to further aid tissue collection, wrinkles or othersurface features may be added to the surface of the balloon. Wrinklesmay form as the balloon deflates to create multiple edges and/oroverlapping material, to aid in cell collection. Edges may work in amanner similar to the edges of a curette or edges of jaws in a biopsyforceps. Similar to these features on other collection devices, edgesformed by the wrinkled balloon may focus a contact force on theanatomical wall in order to collect cells.

The balloon deployment device in accordance with the present disclosuremay then be removed from the working channel of the hysteroscope andfrom the patient. Once the device is removed from the patient, cells maybe removed from the balloon by dipping the balloon and/or the extendingportion (if used) into a cytopreservative and stirring in order toagitate the cells. Alternatively, balloon, extending portion, and/orsheath may be cut off and placed into a cytological preservative. Insome embodiments a sheath may be extendable and deployable over theballoon as the balloon is deflated and removed to protect tissue samplescollected on the balloon surface.

FIG. 24 illustrates a cross-sectional side view of a balloon tipcatheter 160′ including a superelastic push rod 175 and spiral carrier176. The spiral carrier may minimize and/or eliminate the need to extendthe push rod backwards, e.g., outside of a handle, for the full lengthof the push rod in accordance with embodiments of the disclosure. Thepush rod 175 may be constructed of a superelastic material such asNitinol (nickel-titanium compound) wire. At least a portion of a lengthof push rod 175 may be coiled into a spiraling tubular carrier 176,which may be made of polyethylene or polytetrafluoroethylene (Teflon).The outer spiral diameter of the carrier may be approximately 8 cm,rendering the proximal operating length of the catheter handle much morecompact. The spiral carrier 176 may be attached to a proximal seal 135on the catheter by a flexible strap 177. In some embodiments, theflexible strap 177 may be constructed of polymer or silicone rubbermaterial. In some embodiments the push rod 175 may have a diameter ofapproximately 0.025″, or some other thin diameter, which may bedisadvantageous for purposes of gripping the wire and push it forwardthrough the seal 135. A flexible grip 178 may be included that slidesfreely on the push rod 175, but upon compression between the thumb andforefinger, may provide a grip for push rod 175 advancement. Theflexible grip 178 may be an elliptical cross-section frame that may bemade of polyvinyl chloride, silicone rubber, or combinations thereof, orsimilar flexible compound. In some embodiments, the flexible grip mayhave inner dimensions of approximately 2 cm in length, 1 cm in width,and 3 mm in height, and may have a wall thickness of approximately 2 mm.Holes in the proximal and distal faces of the grip may be a slip fitwith the push rod 175.

FIG. 25 illustrates an exemplary embodiment of a balloon tip catheter200 configured with handle 202. In embodiments, the handle 202 may beincluded in the device 160 as illustrated in FIG. 23A. The handle 202may house a gear mechanism 220 (see FIGS. 26A-26B), also referred toherein as an actuator. The handle 202 may be in mechanical communicationwith a push wire 134, 206 and may control actuation of the push wire134, 206, which in turn may control actuation of the balloon 130 betweenan inverted position and an everted position. Handle 202 may include adrive wheel 204 for advancement and retraction of the push wire 134,206, in which the balloon 130 may evert linearly (e.g., gradually unfoldor unroll from the inside out.). The drive wheel 204 may be made ofpolymer material including but not limited to ABS. The outer edge of thedrive wheel 204 may include notches, or a knurl pattern, to facilitategripping the wheel during operation of the catheter 200. The outer edgeof the drive wheel 204 may include multiple features shaped like arrowheads that facilitate gripping and/or may indicate correct direction oftravel of the drive wheel. A top surface of the drive wheel 204 may havean arrow molded into it for indication of a correct direction in whichto turn in order to evert the balloon. The opposite side of the drivewheel 204 may include a square boss 222 insertable into a drive gear224. In some embodiments, the gear mechanism 220 may include a step-downgearing that provides a reduced amount of extension of the push wire134, 206 relative to a given rotational distance traveled by the drivewheel 204 (i.e., the drive wheel 204 must be turned more of a distanceto accomplish the same extended length of balloon everted, than ifstep-down gears were not included or a different ratio of step-down wasincluded). The resultant effect may be to have a finer control over theeversion of the balloon 130 as the drive wheel 204 is turned.

The catheter 200 may retain the balloon 130 in a shaft 210 (which may atleast partially be formed of a stainless steel tube and/or a Nylontube), a sheath 212, and/or a sheath knob 214. For balloon advancement,the balloon 130 and shaft 210 may be pressurized with an inflationdevice (such as inflation device 172 of FIG. 23C) that is attachable toan extension tube 168, 216, or to luer 218, of the handle 202 (see FIGS.26A-26B). Once the catheter device 200 is pressurized, a user may rotatethe drive wheel 204 causing a push wire 134, 206 to advance. Although insome embodiments, the balloon 130 may evert under pressurization withouta drive wheel advancement of the push wire 134, 206, it is understoodthat the drive wheel may allow for smooth, slow, controlled advancementof the balloon, thereby minimizing or avoiding potential perforation ofthe Fallopian tube. The sheath knob 214 may allow the sheath 162, 212 tobe used as an introducer as the sheath 162, 212 locks onto the body ofthe catheter 126, 210. The sheath knob 214 may be compliant enough toallow the user to move the sheath 162, 212 when needed, for example tothe pre-extended portion of the balloon and to move the pre-extendedportion of the balloon into the Fallopian tube. In embodiments, thesheath knob 214 may be tight enough such that unintended balloon orcatheter movement may be minimized and/or prevented.

FIG. 26A is a cross-sectional view of the handle portion of FIG. 25, andFIG. 26B is a detail view of an exemplary embodiment of an internalhandle gear mechanism 220 in accordance with the present disclosure. Thehandle 202 may also have an extension tube 168, 216 that is attached toa luer 218 in the handle body, e.g., for attaching one or moreadditional tools or devices such as inflation device 172 (see also FIG.23C). The gear mechanism or actuator 220 may be in mechanicalcommunication with the push wire 134, 206, and may control actuation ofthe push wire 134, 206, which in turn may control actuation of theballoon 130 between the inverted position and the everted position. Insome embodiments, the gear mechanism or actuator 220 may include aplurality of gears operating enmeshed to have a step-down ratio.According to various embodiments, the handle gear mechanism 220 mayinclude a drive wheel 204, which allows controlled actuation of the gearmechanism 220 and single user operation. The loop “A” as shown in FIG.26A may be included in the handle 202 and the feature for positioning afinger “B” may allow for a user to hold the handle 202 in more than oneposition and may allow for comfortable use of the device no matter thehand size of the user. For example, if the palm of the user's hand is onthe top of the handle “C”, the fingers of the hand may wrap around theinside of the loop “D” for a small hand, or the outside of the loop “E”for a large hand.

In some embodiments, the drive wheel 204 may have a square bossinsertable into square hole 222 in the drive gear 224. The drive wheel204, operable by a medical professional, may be rotatable so that thesquare boss may cause drive gear 224 to rotate. In embodiments, thedrive gear 224 may be rotatable in a direction indicated by arrow 224Aby the drive wheel 204 (see FIG. 26B). The drive gear 224 may engage anidler gear 226 and first gear 228, causing these gears to rotate. Forexample, the first gear 228 may rotate in a direction indicated by arrow228A, which may be a direction opposite of arrow 224A. Likewise, theidler gear 226 may rotate second gear 230 in a direction indicated byarrow 230A, and third gear 232, in a direction indicated by arrow 232Ain response to rotation of the second gear 230. The push wire 206 mayextend between surfaces on and between each of the four gears (224, 228,230, 232), which may each rotate as shown by arrows 224A, 228A, 230A,232A in FIG. 26B during advancement of balloon 130 (e.g., in a distaldirection) via the push wire 206. In some embodiments, gear surfaces maybe formed of a material having a high coefficient of friction such asnatural or silicone rubber, or polyurethane.

The balloon 130 may be advanceable until a proximal end of the push wire134, 206 passes between the drive gear 224 and may be in mechanicalcommunication with first gear 228. Once the push wire 134, 206 haspassed beyond the gear mechanism 220, further rotation of the drivewheel 204 may not advance the balloon 130 further. The absence of thepush wire 134, 206 in the gears 224, 228, 230, 232 may be felt by theuser as a tactile indicator of the balloon 130 being fully everted. Thegear mechanism 220 by being in mechanical communication with the pushwire 206 may allow for fine, precise, and controllable movement for thedeployment and/or retraction of the balloon 130 through eversion andinversion, respectively. As mentioned, the drive wheel may provide forslow and uniform movement for minimizing a potential of perforating theFallopian tube, or inability to navigate the Fallopian tube. The gearmechanism 220 may be a 4 to 1 gear ratio, or a 2 to 1 gear ratio, and itis understood that any other gear ratios may be used to provide controlof the advancement of the balloon. A gear ratio may be configured toprovide slow gear rotation. This may ensure that the deployment speed ofthe balloon is controlled (e.g., slow and uniform) across users, therebyincreasing safety by reducing the risk of adverse events such asperforation.

In some embodiments, to provide feedback to the physician regarding theend of balloon deployment, the internal handle gear mechanism 220 oractuator may include a limit mechanism on the gears for limiting theadvancement of the push wire and/or a unidirectional balloon movement.In some embodiments, the limit mechanism may include at least one of ahard stop, a gear jam, a rack and pawl gear, a linear gear, or a dropkey-click in mechanism. At a predefined maximum extension, a pawl 242may engage with one or more gears (e.g., gears 224, 228, 230, 232) asshown in FIG. 26E, to form a gear jam. The pawl 242 may be activated tostop further advancement of the balloon 130. In embodiments, the pawl242 may be any mechanism configured to engage with one or more gears.For example, at a predefined push wire extension, the pawl 242 mayrotate around a pivot point to engage with one or more gears, causing ajam and preventing further rotation. Alternatively, a rack and pawlgear, a linear gear, or a drop key-click-in mechanism (FIG. 26D) may beemployed to stop advancement of the balloon and in some embodiments maybe disposed in the handle (see FIG. 26A, detail “F”). Referring to FIG.26C, an exemplary ratchet mechanism for linear motion is shown. Ratchetsare mechanisms that serve to limit motion to only one direction. Aratchet may have three main parts: a linear gear rack 233, a pawl 235(e.g., a “click”), and a base or mount 237. The edges on one side of theteeth 239, 239′ on the linear rack may have a steep slope while theother edges of the rack's teeth may have a moderate or gradual slope.For example, edges on one side of the teeth 239, 239′ may be steeperthan edges on another side of the teeth 239, 239′. In some embodiments,a steeper slope may have an angle of approximately 60°-90°, e.g., asindicated at 239 a, 239 a′, and a more moderate slope may have an angleof approximately 10°-50°, e.g., as indicated at 239 b, 239 b′. The pawl235 may contact the linear gear rack 233. When the linear rack islinearly moved in a first direction, the pawl 235 may slide over theteeth 239 without restricting the natural motion of the device. When thedirection of motion is reversed to a second direction, the pawl 235 maycontact the steep slope on the gear tooth 239 to impede motion. The pawl235 may be biased downward by a spring into the linear gear rack 233. Insome embodiments, a spring, e.g., a torsional spring, may be disposed ata pivot point 236, e.g., at a first end of pawl 235, for pivotablerotation of the second end of the pawl 235. In some embodiments, aspring, e.g., a linear spring, may be disposed at a second end of thepawl 235, as indicated by reference numeral 223, to bias the pawl 235towards the gear teeth 239. The linear gear rack 233 and pawl 235 may betypically mounted in a fixed relationship to one another on a mount 237,with the rack sliding in relation to the mount and the pawl 235 having apivot connection to the mount. In some embodiments, the device mayinclude a manual knob or push button switch to overcome the spring biason the pawl 235 to allow for the lifting of the pawl 235 from the set ofteeth on the linear gear.

A limit may be set on the ratcheting action of the linear gear rack 233in the gear mechanism 220 of FIGS. 26A-26B to set a limit on theadvancement of the push wire 206, e.g., as shown at “F”. Duringadvancement of the push wire 206, a pawl 238 may be biased toward fromlinear gear rack 233 as shown in detail “F” of FIG. 26A. In someembodiments, the pawl 238 may be pivotal about a point, as indicated byreference numeral 221. Linear gear rack 233 may be directly attached tothe end of the push wire 206 away from the balloon 130 in the handle202. Advancement of the push wire 206 may be automatically stopped whenpawl 238 meets stop 243, which may be greater in height than teeth 239′.A manual knob or push button switch 205 as illustrated in FIG. 25 may beactuatable by a user to overcome a spring bias on the pawl 238 to allowfor the lifting of the pawl 238 from the linear gear rack 233 and forretraction of the push wire 206 and the attached balloon 130. In FIG.26D, in another embodiment different from the ratcheting action of thelinear gear rack 233, the push wire 206 may be continuously and smoothlyadvanced and coiled around deployment wheel 245 until pawl 235 reachesand engages with detent 247 to stop further advancement of the balloon130. In FIG. 26E, the pawl 235 may act as a gear jam when an extensionlimit of the balloon 130 is reached.

The sequence of steps used to enter and track through the Fallopian tubemay be described with the embodiment of FIG. 23A. When it is desired tocross the UTJ with a length (e.g., approximately 15 mm) of an evertedballoon 130, the outer sheath 162 may be placed in apposition with theproximal os of the Fallopian tube, without entering the proximal os. Theouter sheath 162 may support the initial length of everted balloon 130until it enters the proximal os. A portion of the balloon, e.g., a shortlength, of pressurized everted balloon 130 exiting the supportive outersheath 162 may have sufficient column strength to be manuallyadvanceable through the UTJ, whereas an unsupported length (e.g.,without the sheath) of the everted balloon 130 may not containsufficient rigidity by itself. As such, an everted/everting balloon 130may buckle upon attempted advancement through the proximal os and UTJwithout a sheath. In some embodiments, crossing the UTJ with a length ofthe everted balloon (e.g., 15 mm), may occur. This initial cannulationlength may support keeping the Fallopian tube open even if a spasmoccurs, which may occur in this area of the Fallopian tube. It is alsounderstood that other cannulation lengths may be utilized to maintain anopen Fallopian tube.

In some embodiments, the sheath 162 may be compatible with standardhysteroscopes having a working channel, e.g., 5F. A sheath 162 may beused in an exemplary system as a balance to provide a wall thicknessgreat enough to impart sufficient column strength to the sheath and thinenough to maintain a sheath inner diameter large enough to accommodatethe balloon 130. This balance may improve cell collection efficiency,e.g., by having an inner diameter sufficient to retain the balloon 130without inadvertently removing (scraping) cells from the balloonsurface. It is understood that the balloon 130 may be retained withinthe sheath 162 in an inflated state and/or a deflated state.

As mentioned, a male luer lock fitting, or sheath knob, 164 including aTuohy-Borst seal 136 connector may be included at the proximal end ofthe sheath 162. A Tuohy-Borst adapter that includes seal 136 is amedical device used for creating seals between devices and attachingcatheters to other devices. The Touhy-Borst seal 136 may be tightened tohave a slip fit with the catheter or cannula holding the sheath 162 inplace. The sheath knob 164 may mate with a female luer lock fitting, ifpresent, at an instrumentation port, on the working channel of thehysteroscope 20. Referring back to FIG. 3, the male luer lock or sheathknob 164 may be connectable to the instrumentation port 23 so that thecatheter 126 and/or sheath 162 may move with the hysteroscope 20. Insome embodiments, the instrumentation port 23 may further include a sealfor the catheter 126 to extend through. When these respective luerfittings are connected, the tip of the sheath 162 may protrude out ofthe distal end of the hysteroscope, e.g., approximately 2-3 cm. Thesheath 162 may also protect a portion of a balloon 130 everted duringdevice preparation (e.g., a length approximately 1.5 cm) from injury asthe catheter 126 is advanced through the working channel of thehysteroscope. A stainless steel tube, e.g., hypotube 138, may be atleast a portion the inner cannula 126 to provide sufficient rigidityand/or column strength to minimize or prevent kinking of the portionprotruding from the proximal end of the hysteroscope working channel. Insome embodiments, the hypotube 138 may be sized having approximately0.050″ OD×0.004″ wall thickness for sufficient rigidity.

In some embodiments, the hypotube 138 may ensure that the handle 202 isundisturbed, or does not fall out of the working channel of thehysteroscope 20 when a medical professional releases the device during aprocedure. The sheath 162 may be coaxial with the tube or catheter 126and may be slidably adjustable to cover at least a first length of theballoon extending outward from the distal end in the everted position.The sheath 162 may form a physical barrier and may protect the balloonin at least one of the inverted position, a partially everted position,and/or a fully everted position and may serve to protect collected cellsfrom dislodgement during transit out of the patient body.

As mentioned, at least a portion of each of the sheath 162, a portion ofthe tube or catheter 126, and/or the balloon 130 may be translucent,optically transparent, or a combination thereof, to facilitate visualfeedback of relative positions of the aforementioned device componentsduring deployment and retraction. It is understood that a hysteroscope20 may be well suited for visual observation of a cell collection withthe device. Translucency and/or transparency of a device component maybe dependent on the observational wavelengths. By way of examplethermoplastic materials can appear clear under visible light, yet areopaque to other portions of the electromagnetic spectrum.

FIG. 23C illustrates a balloon tip catheter 160 of FIG. 23A with atubing reservoir, or extension tube 168, and inflation device 172 inaccordance with an exemplary embodiment of the disclosure. It isunderstood that in some embodiments the extension tube 168 may besimilar to extension tube 216 as shown in FIG. 26A. The extension tube168, 216 may be configured to withstand pressurization. Pressurizationof the balloon 130 by fluid injection may be performed using a syringedevice, such as the exemplary inflation device 172. Rotation of athreaded plunger shaft through a releasable lock may increase andmaintain pressure in the inflation device 172, while a pressure gauge174 provided with the inflation device 172 may allow for control ofinput pressure. In some embodiments, the balloon tip catheter 160 mayprovide for a one-person operation of the device. A length of pressuretubing, or extension tube 168, 216, may be added between the inflationdevice 172 and the inflation port 166 on the device. The extension tube168, 216 may be constructed of polymers such as polyurethane orpolyvinyl chloride (PVC), with or without polymer or metal coil or braidreinforcement. The extension tube 168, 216 may contain an amount ofintrinsic elasticity, while the everting balloon may be generallyinelastic. At full pressurization of the balloon 130, the extension tube168, 216 may impart a fluid capacitance to the system. A small volume offluid may be containable in the everted balloon, and this volume may befurther subtracted by the volume occupied by the push rod 134 (e.g.,which moves into the balloon 130 as it is being everted). The resultanteverted balloon volume may be small compared with the larger volume inthe pressure tubing 168, which may allow the balloon 130 to evert to itsfull length without significant decrease in pressure, once the balloontip catheter 160 has been pressurized.

A length of an extension tube 168, 216 may be added between theinflation device 172 and the inflation port 166 on the device inresponse to positioning a stopcock valve 170 in a location proximal, oraway, from the device and the hysteroscope 20. For example, as shown inFIG. 25, luer 218 may connect pressure tubing 168, 216, for connectionwith a stopcock valve 170. In embodiments, a stopcock valve 170 may bedisposed at an end of extension tube 168, 216 for connection with a luer219 and the inflation device 172. In some embodiments, the stopcockvalve 170 may be connected to the luer 218. The stopcock valve 170 maybe closed following pressurization, and the inflation device 172 may beremoved from the examination field, prior to insertion and eversion ofthe balloon 130. This one-operator procedure may be less cumbersome andmore efficient during a medical procedure. It is also understood that insome embodiments, the luer 219 may be connectable to the inflationdevice 172 without a stopcock valve 170.

As described above with respect to FIGS. 23A-23C, the everting balloon130 may be extendable a total distance of approximately 7 cm distal tothe tip of the catheter, in order to pass through the entire length ofthe Fallopian tube. The everting balloon 130 may form a toroidal shapeat the end 130 a as it exits the catheter tip, and the everted portionmay include a double walled configuration. A toroidal shape may be anatraumatic shape for minimizing or avoiding damage during extension intothe Fallopian tube. Thus, for example, the push rod 134 advances forwarda distance of approximately 14 cm in order to yield an everted balloonlength of 7 cm. This length of push rod may initially extend backwardsfrom the proximal end of the catheter 126, directly into the face of theoperator, making its use cumbersome. The push rod may also besusceptible to contamination of the sterile device due to its length asit may extend into a physician's working space during a procedure. Forexample, the proximal end of the long push rod 134 may contact thephysician's face or surgical mask during use. Therefore, it may bedesirable to provide a push rod system that does not have to extendbackwards for the full length of the push rod 134. The superelastic pushrod 175 and carrier design of FIG. 24 and the balloon tip catheter 200configured with handle 202 of FIG. 25 may contain the push rod andminimize and/or avoid the need to extend the push rod back towards theuser.

FIG. 27 illustrates a cross-sectional side view of an exemplary evertedballoon tip catheter 180 including a tube 182 having diameter smallerthan the inflated diameter of the everting balloon 130 for insertioninto the patient's UTJ in accordance with the present disclosure. Thetube 182 may straighten a portion of the balloon tip 163. In someembodiments, the tube 182 may extend distally to the tip of the cannula.In embodiments, the tube 182 may have an approximately 0.0005″-0.001″wall thickness (e.g., being a “thin-walled” tube), and may extendapproximately 1.5 cm distal to the tip of the cannula. The tube 182 mayhave a thickness and resiliency sufficient to support the balloon 130,to maintain a position of the balloon tip 163 (e.g., maintain a straightposition). In some embodiments, the tube 182 diameter may be smallerthan the balloon 130 diameter, so that the balloon 130 may retainflexibility and compressibility. This flexibility may be beneficial toallow the balloon 130 to be advanced through the UTJ. In someembodiments, the balloon 130 may include the tube 182 to support and/orstraighten the balloon. In embodiments, the tube 182 may have a 0.033″OD×0.001″ wall×1.5 cm long.

FIG. 28 illustrates a cross-sectional side view of an everted balloontip catheter 190 including one or more flexible polymer monofilamentstring and/or suture 192 as an extending portion attached to the distalend of the cannula or catheter 126. The strands 192 may extend intoeverting balloon tip 163, thereby supporting and keeping the tipstraight for insertion into the patient's UTJ in accordance with anembodiment of the present disclosure. In some embodiments, the one ormore flexible polymer monofilament string and/or suture 192 may extendinto the balloon tip 163 (e.g., approximately 1.5 cm). The monofilament192 may be formed of nylon, polypropylene, or other flexible polymermaterial, or combinations thereof. The monofilament strands may have adiameter of approximately 0.006″-0.012″. In some embodiments, theballoon 130 may have approximately a 0.033″ (0.8 mm) OD with a 0.008″diameter monofilament 192 inside an approximately 1.5 cm long evertedballoon tip.

FIGS. 29A-29C illustrate a steerable balloon tip 252 for an evertedballoon catheter 250 using guide wires in accordance with an exemplaryembodiment of the present disclosure. As shown in FIG. 29A a steerableballoon tip 252 may be controllable by a right direction guide wire 254and a left direction guide wire 256. In FIG. 29B the right guide wire254 may be manipulated (e.g., pulled, as shown by the arrow 255) tosteer the balloon tip 252 to the right. Conversely, in FIG. 29C, theleft guide wire 256 may be manipulated, (e.g., pulled, as shown by thearrow 257) to steer the balloon tip 252 to the left. It is noted thatadditional guide wires may be included to provide movement in theZ-plane in addition to movement in the X-Y plane achieved with the pairof guide wires as shown.

FIG. 30 illustrates a side perspective view of a balloon catheter 260having a smaller diameter lead balloon tip 262 at the distal end of theeverted balloon 130 in accordance with an exemplary embodiment of thepresent disclosure. The smaller diameter lead balloon tip 262 may bedimensioned so as to gradually expand the opening at the constriction ofthe UTJ, while being flexible with blunted edges so as not to perforatethe walls at the UTJ.

FIG. 31 illustrates a side perspective view of a balloon catheter 270with a flexible guide wire 272 on the tip of the balloon 30 inaccordance with an exemplary embodiment of the present disclosure. Theflexible guide wire may lead the balloon catheter 220 through the UTJinto the Fallopian tube.

In embodiments, a portion of the everted balloon may be treated withfluoropolymer, silicone, and like material coatings, or combinationsthereof, lubricating the surface at the lead portion of the ballooncatheter, which may enter the constricted portions of the Fallopian tube(e.g., the UTJ).

FIG. 32 illustrates a partial side perspective view of a striped balloon130S prior to inversion of the striped balloon 130S into the catheter orcannula of FIG. 32 in accordance with an embodiment of the disclosure.The indicia 131 on the balloon provide a visual feedback indicator ofthe progress of the balloon eversion. In a specific embodiment, theindicia 131 may be approximately 1 mm wide and spaced at approximately 1cm increments along the entire length of the balloon 130S. Alternativespacing of the strips or other visual markers on the balloon may bespaced closer together for finer positional feedback, or further apartfor coarser feedback. Other visual markers of length of eversion mayinclude sinusoidal indicia with a known length of periodicity. It isalso appreciated that indicia of length may also include differentlycolorized segments of a known length.

FIG. 33 illustrates a cross-sectional side view of a balloon tipcatheter 280 configured with striped balloon 130S in accordance with anexemplary embodiment of the present disclosure. As shown in FIG. 33, theindicia 131 of the striped everting balloon 130S may be coupled with atransparent distal section 167 of the cannula or catheter 126 to providevisual feedback of balloon eversion. In some embodiments, the indiciamay be pad printed or scribed with an indelible marker in a highlyvisible color. In some embodiments, the indicia 131 may be approximately1 mm wide, spaced approximately in 0.5 cm increments along the entirelength of the balloon. Pad printing (also called tampography) is aprinting process for transferring a 2-D image onto a 3-D object. Otherpatterns may be used instead of, or in addition to, indicia 131 on thesurface of the balloon 130S. For example, indicium 131 on the balloon130S may be spaced apart (e.g., approximately 0.5 cm), and dots may alsobe added in the remaining intervals between the indicia 131. Eachindicium 131 that comes into view in the transparent distal section 167may indicate a successful eversion of a length of a balloon 130S (e.g.,0.25 cm, as the push rod is advanced approximately twice the length fora corresponding approximate length of balloon eversion (e.g., 0.5 cm).Indicia 131 of different thicknesses may be used, as well as differentcolored indicia, or a different number of indicia, or combinationsthereof, in the same fashion described for the stripe and dotcombination. In some embodiments, color coded sections may be added tothe balloon 130S to indicate the extent of the balloon eversion.

Additional embodiments of feedback markers, which may be externallyvisible to the physician on the outside of the patient's body, for theextent of positive balloon eversion. In some embodiments, a knottedstring or braided sutures as an extending portion may be adhered to thedistal end of the push rod or tip of the balloon, and may be spaced inknown increments to provide tactile feedback as to balloon eversionprogress. The knotted string or braided sutures may allow forvisualization of the forward movement of the balloon as it is everted.The knotted string or sutures may be radio opaque. The string may havecolor coded zones for providing visual feedback to the operator. Toenhance visualization of the knotted string or braided sutures, thesutures, indicia, or color-coded zones may be provided in a highlycontrasting color from the catheter and anatomy. In some embodiments,the braided surface of the sutures may assist with collection and/orretention of cells due to the texture and folds of the braid. Forexample, tissue and/or cells may become embedded in the texture and/orfolds of the braiding. In some embodiments shown in FIG. 34A, a string140 may be pad printed with indicia 131 in a similar manner to theballoon as noted above in FIGS. 32 and 33. FIG. 34B illustrates a string140′ with a series of knots or sutures 142. The balloon 130 may be atleast partially transparent to enhance visibility of string, indicia,knots, or sutures.

In some embodiments, the string as an extending portion may be braidedas shown in FIGS. 11C and 11D. The braided string, knots, or sutures mayalso provide an additional cell collection surface. In some embodiments,cells may be collected and retained within the braiding of the suture43, which may be advantageous over cells collected only on a suturesurface. Cells collected within the braiding of the suture 43 may beless likely to be inadvertently removed or wiped away during retractionof the suture 43 and/or balloon 32, as cells may be collected betweenbraiding, thereby providing protection of the collected cells.

In some embodiments, different strands of the string or suture may beformed of different colors, shades, or thicknesses, relative to otherstrands, as shown in FIGS. 11E and 11F. For example, as shown in athree-strand suture in FIG. 11E, strands 47 and 49 of suture 46 may be adifferent color or darker shade as compared to strand 51. Alternatively,as shown in FIG. 11F, strands 47′ and 51′ of suture 46′ may be adifferent color or lighter shade as compared to strand 49′. The strands47, 47′, 49, 49′, 51, 51′ may be formed of a selected color along anentire length, so that when in a braiding pattern, a medicalprofessional may be able to visualize a color contrast, or distinction,along the length of the braid in predetermined segment lengths. Forexample, a first strand 47, 47′ may extend on an outer portion of thesuture 46, 46′ (e.g., braid) for a length L1, L1′ every third portion, asecond strand 49, 49′ may extend on an outer portion of the suture 46,46′ for a length L2, L2′ every third portion, and a third strand 51, 51′may extend on an outer portion of the suture 46, 46′ for a length L3,L3′ every third portion. For visual clarity, the strands are shown oflike thickness, although it is understood that the strings, knots,sutures may be any thickness, and may be equal thicknesses, or differentthicknesses. In other embodiments, the fibers within a given strand mayhave a color difference relative to the remainder of the strand.

An advantage of varying the appearance of strands along a length of thesuture 46, 46′ is that the appearance of the string or suture may varyalong the length, providing feedback to the operator that the respectivestring or suture is moving and the balloon is everting. For example, amedical professional may be able to visualize movement of the suture bythe color contrast of the suture 46, 46′. String or sutures may also betreated with surface modifications such as plasma, corona, or nanofibersurface application to modify surface properties thereof. Additionally,the braided string, knotted string, or sutures may also provideadditional tensile strength for the balloon in that the string orsutures may act to absorb and dissipate forces acting on the balloon,thereby reducing the risk of the balloon detachment.

Additional feedback mechanisms may include filling the balloon 130 withagitated saline and visualizing air bubbles with ultrasound, and asinusoidal pattern for the balloon, where the distances between maximumsof a sinusoidal wave define an incremental distance of balloon eversion.

Navigation within the Fallopian tube and the indication of a clear pathor obstructions may be provided by release of microbubbles from the tipof the balloon or from the distal end of the tube that the ballooneverts from. Travel of the microbubbles may be trackable using imaging,such as ultrasound, to ascertain where a clear path exists. In instancesof an obstruction 251, e.g., an occlusion or a constriction, themicrobubbles may bunch up, or congregate, when the microbubbles areimpeded. In response to detecting a grouping of microbubbles, a medicalprofessional may be able to ascertain an obstruction. FIG. 36Aillustrates a release of a stream of microbubbles 249 from a tip of theballoon 130 in the Fallopian tube 1 where no constrictions orobstructions are present, as evident by the steady continuous line ofmicrobubbles 249. In some embodiments, microbubbles may be deliveredthrough an inner lumen 54 of a balloon, as shown in FIGS. 17A-17B. Thefrequency or spacing of the microbubbles 249 may be controllable forfiner measurements than with an air source that is modulated on or off,where the air is introduced to the fluid injected into the balloon 130.FIG. 36B illustrates a Fallopian tube 1 with a tubular constriction orobstruction 251, where the tubular constriction or obstruction 251 mayimpede a flow of microbubbles 249 and the microbubbles 249 begin tocongregate, or bunch up, at the point of the constriction or obstruction251. The bunching of the microbubbles 249 may provide a visualindication to the user where the constriction or obstruction 251 is inthe Fallopian tube 1. In response to a detected obstruction 251, amedical professional may perform additional imaging, such as ultrasound,to determine where the balloon stopped.

The present disclosure further provides various methods for collectingcells from a lumen of a subject using embodiments of the catheterdescribed above. Methods may include using a catheter including at leasta tube, a balloon (with or without an extending portion) secured to adistal end of the tube, a push wire that actuates said balloon betweenan inverted position within the tube and an everted position extendingbeyond the distal end, and a slidable sheath coaxial with the tube,everting a first portion (approximately 1 to 2 cm according to someembodiments) of the balloon distally beyond the distal end of the tubeto the preselected distance, positioning the sheath and everted firstportion of the balloon proximate to the lumen of a subject, orcombinations thereof.

The balloon may be inflated, or otherwise pressurized, for initialeversion of the balloon to occur. For example, by pressurizing theballoon, column strength may be provided to the balloon, allowing it toevert when a push wire is advanced. The sheath knob may be advanced tothe first marker on the hypotube and/or catheter. The balloon may beeverted to the point at the distal tip of the sheath. The distal tip ofthe sheath, and the pre-extended balloon, may be placed proximal to theostium of the Fallopian tube. The sheath may be held in place bymaintaining the sheath knob in a selected position, and the balloon andcatheter may be further advanced, so that an initial portion of aneverted balloon is inserted into the proximal os.

A medical professional may rotate a drive wheel for further eversion ofthe balloon and/or the suture as an extending portion. The drive wheelmay be rotated until the balloon and/or suture is partially or fullyeverted. In some embodiments, a final everted length (e.g.,approximately 7-12 cm) may be approximately equivalent to half of pushwire travel. When the balloon and/or the suture is fully everted, thedistal end of the push wire may remain in the catheter and may notcontact the Fallopian tube.

The inflated balloon as fully everted in the Fallopian tube may fill thepotential space of the Fallopian tube, contacting an inner surface ofthe Fallopian tube. The surface area contact may transfer cells onto theballoon surface. The balloon may be deflated while everted in theFallopian tube, so that wrinkles in the balloon surface may capturecells collected on the balloon surface. In some embodiments, the balloonmay be cycled between inflated and deflated while everted, forpotentially increasing cell collection on the balloon surface and withinthe balloon surface features. In some embodiments, the suture may extendfrom the fully everted balloon, further collecting cells on the suture.

When cell collection on the balloon surface and/or the suture iscomplete, the medical professional may retract the handle of the devicewhile holding the sheath in place, so that the everted balloon and/orthe suture may be retracted within the sheath. A marker on the tube ofthe catheter when aligned with the sheath knob may provide an indicationthat the full length of the balloon/extending portion has been retractedwith the sheath. The sheath may protect the collected cells on theballoon surface and/or the suture, for removing the device from theworking channel of the hysteroscope.

By inserting the everted first portion of the balloon into the lumen,and further everting the balloon into the lumen using the push wire,cells may be collected on the balloon. Some embodiments of the methodmay also include adjusting a speed of the further everting step relativeto the inserting the everted first portion of the balloon into the lumenstep. A marker on the tube of the catheter when aligned with the sheathknob may provide an indication that the full length of theballoon/extending portion has been retracted with the sheath.

Any patents or publications mentioned in this specification are hereinincorporated by reference to the same extent as if each individualpublication was specifically and individually indicated to beincorporated by reference. The foregoing description is illustrative ofparticular embodiments of the disclosure, but is not meant to be alimitation upon the practice thereof.

Numerous specific details have been set forth herein to provide athorough understanding of the embodiments. It will be understood bythose skilled in the art, however, that the embodiments may be practicedwithout these specific details. In other instances, well-knownoperations, components, and circuits have not been described in detailso as not to obscure the embodiments. It can be appreciated that thespecific structural and functional details disclosed herein may berepresentative and do not necessarily limit the scope of theembodiments.

Some embodiments may be described using the expression “coupled” and“connected” along with their derivatives. These terms are not intendedas synonyms for each other. For example, some embodiments may bedescribed using the terms “connected” and/or “coupled” to indicate thattwo or more elements are in direct physical or electrical contact witheach other. The term “coupled,” however, may also mean that two or moreelements are not in direct contact with each other, but yet stillco-operate or interact with each other.

It should be noted that the methods described herein do not have to beexecuted in the order described, or in any particular order. Moreover,various activities described with respect to the methods identifiedherein can be executed in serial or parallel fashion.

What is claimed is:
 1. A device for Fallopian tube diagnostics,comprising: a tube having a distal end; a balloon having a first endcoupled to the distal end of the tube, the balloon being disposed in thetube in a first, inverted position, movable to a second, evertedposition, and extendable a distance distal of the tube; and a singleextending portion having a proximal end directly coupled to andimmediately adjacent a second end of the balloon at a single area ofcontact, wherein the extending portion comprises any of a filament,suture, or string, or combinations thereof; where the balloon onlycouples to the single extending portion at the second end of the balloonand lateral surfaces of the balloon do not couple to additionalextending portions; and wherein the extending portion is disposed withinthe balloon in the first inverted position, and is extendable from thesecond end of the balloon in the second everted position.
 2. The deviceaccording to claim 1, wherein at least a portion of the filament,suture, or string, or combinations thereof, is braided.
 3. The deviceaccording to claim 1, wherein the extending portion is formed of one ormore filaments having a color, wherein the colors of the one or morefilaments of the extending portion are configured to provide for acontrasting visualization.
 4. The device according to claim 1, whereinthe extending portion includes one or more knots or indicia for one orboth of visual and tactile feedback.
 5. The device according to claim 1,wherein the extending portion is a braided filament configured tocollect and retain a tissue sample in response to extending from theballoon in the second everted position.
 6. The device according to claim1, further comprising a push wire having a distal end coupled to thesecond end of the balloon and the proximal end of the extending portion,wherein the balloon and the extending portion are movable from the firstinverted position to the second everted position by actuation of thepush wire.
 7. A system for collecting a tissue sample in a body lumen,comprising: a tube having a distal end, a balloon having a first endcoupled to the distal end of the tube and a second end, and a singleextending portion attached to the second end of the balloon, the balloonand the extending portion being positionable in a first, inverted state;wherein a proximal end of the extending portion is directly coupled toand immediately adjacent the second end of the balloon at a single areaof contact, wherein the balloon and the extending portion are configuredto advance to a second, everted state, such that the balloon and theextending portion extend out of the distal end of the tube; and whereinthe extending portion comprises any of a filament, suture, or string, orcombinations thereof; where the balloon only couples to the singleextending portion at the second end of the balloon and lateral surfacesof the balloon do not couple to additional extending portions; andwherein the extending portion is disposed within the balloon in thefirst inverted position, and is extendable from the balloon in thesecond everted position into the body lumen.
 8. The system according toclaim 7, wherein at least a portion of the filament, suture, or string,or combinations thereof, is braided.
 9. The system according to claim 7,wherein the extending portion is formed of one or more filaments havinga color, wherein the colors of the one or more filaments of theextending portion are configured to provide for a contrastingvisualization.
 10. The system according to claim 8, wherein theextending portion includes one or more knots or indicia for one or bothof visual and tactile feedback.
 11. The system according to claim 7,wherein the extending portion is a braided filament configured tocollect and retain a tissue sample in response to extending from theballoon in the second everted position into the body lumen.
 12. Thesystem according to claim 7, further comprising a push wire having adistal end coupled to the second end of the balloon and the proximal endof the extending portion, wherein the balloon and the extending portionare movable from the first inverted position to the second evertedposition by actuation of the push wire.
 13. A method for collecting atissue sample in a body lumen, comprising: providing a tube having adistal end, a balloon having a first end coupled to the distal end ofthe tube and a second end, and a single extending portion attached tothe second end of the balloon, the balloon and the extending portionbeing positioned in a first, inverted state; advancing the balloon to asecond, everted state, such that the balloon and the extending portionextend out of the distal end of the tube; wherein a proximal end of theextending portion is directly coupled to and immediately adjacent thesecond end of the balloon at a single area of contact, wherein theextending portion comprises any of a filament, suture, or string, orcombinations thereof; where the balloon only couples to the singleextending portion at the second end of the balloon and lateral surfacesof the balloon do not couple to additional extending portions; andwherein the extending portion is disposed within the balloon in thefirst inverted position, and is extendable from the balloon in thesecond everted position into the body lumen.
 14. The method according toclaim 13, further comprising collecting the tissue sample by theextending portion extendable from the balloon in the second evertedposition into the body lumen.
 15. The method according to claim 13,wherein the extending portion is formed of one or more filaments havinga color, wherein the colors of the one or more filaments of theextending portion provide for a contrasting visualization.
 16. Themethod according to claim 13, wherein the extending portion is a braidedfilament configured to collect and retain a tissue sample in response toextending from the balloon in the second everted position into the bodylumen.
 17. The method according to claim 13, further comprisingactuating a push wire having a distal end coupled to the second end ofthe balloon and the proximal end of the extending portion, to move theballoon and the extending portion from the first inverted position tothe second everted position.
 18. The method according to claim 13,wherein at least a portion of the filament, suture, or string, orcombinations thereof, is braided.
 19. The method according to claim 13,wherein the extending portion includes one or more knots or indicia forone or both of visual and tactile feedback.